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Vinorelbine

Web Resources: Vinorelbine
Recent Research Publications

Web Resources: Vinorelbine (6 links)


Recent Research Publications

Aitelhaj M, Lkhoyaali S, Rais G, et al.
First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study.
Pan Afr Med J. 2016; 24:324 [PubMed] Free Access to Full Article Related Publications
Breast cancer is the most common malignant disease and among the most frequent causes of cancer mortality in females worldwide. Metastatic breast cancer (MBC) is conventionally considered to be incurable. In first-line treatment of HER-2 positive MBC, randomized trials have demonstrated that trastuzumab when combined with chemotherapy significantly improves progression free survival and overall survival. To evaluate survival and toxicity of chemotherapy with Trastuzumab as first line therapy of human epithermal growth factor receptor 2 positive metastatic breast cancer, in Moroccan population. It is a phase IV observational institutional monocentric study. Including patients with metastatic breast cancer HER2 positive, as first-line chemotherapy combined with Trastuzumab from March 2009 until March 2010. Primary end point: progression free survival, secondary end point response rate and overall survival. A total of 20 patients were enrolled between March 2009 and March 2010. The lung was the first metastatic site in 60% of the cases, followed by bone, liver, nodes, skin and brain. All patients received chemotherapy with Trastuzumab: 9 of them with Docetaxel, 8 with vinorelbine, and 3 with capecitabine. The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab based chemotherapy was generally well tolerated; 5 patients (25%) presented cardiotoxicity. The results of this study join the literature and show the benefit of Trastuzumab to chemotherapy in first line metastatic breast cancer HER-2 positive.

Fu ZZ, Li K, Peng Y, et al.
Efficacy and toxicity of different concurrent chemoradiotherapy regimens in the treatment of advanced cervical cancer: A network meta-analysis.
Medicine (Baltimore). 2017; 96(2):e5853 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of different concurrent chemoradiotherapy (CCRT) regimens in the treatment of advanced cervical cancer (CC) by adopting a network meta-analysis.
METHODS: We searched PubMed and Cochrane Library from the inception of these databases to September 2016, and all cohort studies (CSs) related to different CCRT regimens in the treatment of CC were included. A network analysis was adopted to compare the combination of direct and indirect evidence, to analyze the odds ratio (OR), and to draw a surface under the cumulative ranking curve of the efficacy and toxicity of different CCRT regimens for CC. Cluster analyses were used to group each category based on similar treatment regimens.
RESULTS: Nineteen CSs were enrolled in this network meta-analysis, including 12 CCRT regimens (radiotherapy [RT], CCRT [cisplatin], CCRT [vinorelbine], CCRT [paclitaxel], CCRT [hydroxyurea], CCRT [cisplatin + FU], CCRT [cisplatin + gemcitabine], CCRT [cisplatin + docetaxel], CCRT [cisplatin + paclitaxel], CCRT [cisplatin + amifostine], CCRT [cisplatin + FU + hydroxyurea], and CCRT [cisplatin + vincristine + bleomycin]). The results of the network meta-analysis showed that regarding efficacy, the overall response rate of CCRT (cisplatin + docetaxel) was higher than RT, and the 5-year overall survival (OS) rate of CCRT (cisplatin + FU + hydroxyurea) was relatively higher than CCRT (hydroxyurea). As for toxicity, CCRT (cisplatin) had a lower incidence of leukopenia than CCRT (hydroxyurea), CCRT (cisplatin + FU) and CCRT (cisplatin + paclitaxel), and the incidences of diarrhea and vomiting in CCRT (cisplatin) were lower than those in CCRT (cisplatin + gemcitabine). Additionally, the cluster analysis showed that CCRT (cisplatin) had relatively lower incidences of both hematotoxicity and gastrointestinal toxicity, and CCRT (paclitaxel) had lower gastrointestinal toxicity than other regimens.
CONCLUSION: Our study demonstrated that CCRT (cisplatin + docetaxel) might be the best choice of CCRT regimens in the treatment of CC, and the 5-year OS rate of CCRT (cisplatin + FU + hydroxyurea) might be the highest among these different regimens. CCRT (cisplatin) might have the lowest toxicity among all the CCRT regimens.

Chisaki Y, Nakamura N, Yano Y
Time-Series Modeling and Simulation for Comparative Cost-Effective Analysis in Cancer Chemotherapy: An Application to Platinum-Based Regimens for Advanced Non-small Cell Lung Cancer.
Biol Pharm Bull. 2017; 40(1):73-81 [PubMed] Related Publications
The purpose of this study was to propose a time-series modeling and simulation (M&S) strategy for probabilistic cost-effective analysis in cancer chemotherapy using a Monte-Carlo method based on data available from the literature. The simulation included the cost for chemotherapy, for pharmaceutical care for adverse events (AEs) and other medical costs. As an application example, we describe the analysis for the comparison of four regimens, cisplatin plus irinotecan, carboplatin plus paclitaxel, cisplatin plus gemcitabine (GP), and cisplatin plus vinorelbine, for advanced non-small cell lung cancer. The factors, drug efficacy explained by overall survival or time to treatment failure, frequency and severity of AEs, utility value of AEs to determine QOL, the drugs' and other medical costs in Japan, were included in the model. The simulation was performed and quality adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. An index, percentage of superiority (%SUP) which is the rate of the increased cost vs. QALY-gained plots within the area of positive QALY-gained and also below some threshold values of the ICER, was calculated as functions of threshold values of the ICER. An M&S process was developed, and for the simulation example, the GP regimen was the most cost-effective, in case of threshold values of the ICER=$70000/year, the %SUP for the GP are more than 50%. We developed an M&S process for probabilistic cost-effective analysis, this method would be useful for decision-making in choosing a cancer chemotherapy regimen in terms of pharmacoeconomic.

Boussios S, Seraj E, Zarkavelis G, et al.
Management of patients with recurrent/advanced cervical cancer beyond first line platinum regimens: Where do we stand? A literature review.
Crit Rev Oncol Hematol. 2016; 108:164-174 [PubMed] Related Publications
BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed.
METHODS: We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies. Our effort was to highlight the available treatment options in the setting of recurrent/metastatic disease.
RESULTS: Although there have been important advances in the management of women with cervical cancer, the optimal treatment for patients with locally recurrent and metastatic disease after platinum failure is still problematic. Overall, there is a trend in terms of longer overall survival (OS) and better quality of life for the combination of cisplatin/paclitaxel (PC) as compared to the doublets of cisplatin/topotecan (TC), cisplatin/vinorelbine (VC), and cisplatin/gemcitabine (GC). Currently available single agents beyond first-line platinum-based therapy have limited efficacy in this setting and include topoisomerase inhibitors, vinca alkaloids, taxanes, alkylating agents and antimetabolites. Several targeted therapies have demonstrated activity in advanced cervical cancer. Bevacizumab has been evaluated in a phase III trial using doublets of cisplatin with paclitaxel or topotecan and has been approved in the first-line setting by the U. S. Food and Drug Administration. Selective targeting of angiogenic kinases by tyrosine kinase inhibitors (TKIs) may represent a novel therapeutic tool in this setting, but its use alone or in combination with CT is still investigational. Early reports have implicated PI3KCA somatic mutations suggesting that mTOR-targeted agents should be explored in this disease. Development of the immune checkpoint programmed cell death 1 (PD-1) and T-lymphocyte-associated molecule-4 (CTLA-4) inhibitors have been of considerable interest, leading to ongoing phase II studies in patients with advanced cervical cancer.
CONCLUSIONS: Progress in the management of recurrent and advanced cervical cancer patients has been slow and restricted to palliative intent. These patients should be considered for clinical trials of novel targeted agents and/or immunotherapy.

Cazzaniga ME, Torri V, Riva F, et al.
Efficacy and safety of vinorelbine-capecitabine oral metronomic combination in elderly metastatic breast cancer patients: VICTOR-1 study.
Tumori. 2017; 103(1):e4-e8 [PubMed] Related Publications
PURPOSE: Elderly patients with metastatic breast cancer are expected to derive similar benefits from chemotherapy as younger patients, but are more likely to experience therapy-related toxicity. Data from the VICTOR-1 study showed that metronomic therapy with vinorelbine and capecitabine was effective and well tolerated in patients with metastatic breast cancer. This analysis determined the efficacy and safety of the metronomic combination of oral vinorelbine and capecitabine in a subgroup of VICTOR-1 study patients aged ≥70 years.
METHODS: Eighteen of the 32 patients enrolled in VICTOR-1 were aged ≥70 years. Objective response and clinical benefit rates were calculated and toxicity was determined using the NCI-CTCAE criteria.
RESULTS: All patients had at least 1 comorbidity (4 had 2 comorbidities), and 77.7% were taking concomitant medication. Eight patients (44%) had received ≥1 chemotherapy regimens for metastatic disease and most (78%) had ≥2 metastatic sites. Grade 1-2 adverse events occurred in 45.8% of cycles, whereas the incidence of grade 3 and grade 4 events was very low (1.5% and 0.7%, respectively). Median time to progression was 10.5 months (range 1-40). The objective response rate was 33% and the clinical benefit rate was 67%.
CONCLUSIONS: The all-oral metronomic combination of vinorelbine and capecitabine had an acceptable efficacy profile and appears to be better tolerated than standard treatment schedules in elderly metastatic breast cancer patients (age ≥70 years).

Wang Y, Liu J, Jia W, et al.
Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer.
Chemotherapy. 2017; 62(1):71-79 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate the efficacy of vinorelbine-based regimens as first-, second- and more-line therapies in advanced breast cancer (ABC) and to analyze the best timing of vinorelbine treatment.
METHODS: A total of 71 ABC patients were retrospectively reviewed. Of these, 35 patients were treated with vinorelbine-based regimens as first-line chemotherapy, and 36 patients were treated with vinorelbine-based regimens as second-line or more-line therapy. The primary end point of the study was progression-free survival (PFS).
RESULTS: No difference was found in baseline characteristics between the two groups (p > 0.1 for all comparisons). There was a significant difference in the objective response rate (ORR; p = 0.006) and clinical benefit rate (CBR; p = 0.013) between the first-line group and the second- or more-line groups. In the vinorelbine first-line group, the ORR was 68.6% (24 patients), and in the second-line or more-line groups the ORR was 36.1% (13 patients). A significant difference in PFS between the first-line group and the second-line or more-line groups was also observed (p = 0.030). The median PFS in the overall population was 6.3 ± 1.32 months (95% CI 3.69-8.90). The median PFS was 11.1 ± 3.76 months (95% CI 3.73-18.47) in the first-line group compared with 5.2 ± 1.35 months (95% CI 2.54-7.85) in the second-line or more-line groups. In patients treated with vinorelbine-trastuzumab combination as the first-line therapy, a complete response was observed in 1 patient (12.5%) and partial response in 5 patients (62.5%), giving an ORR of 75.0%. Progressive disease was observed in 1 patient (12.5%), and stable disease in 1 patient (12.5%), leading to a CBR of 87.5%. The median PFS was 13.8 ± 2.75 months (95% CI 8.42-19.18), and median OS was 37.0 ± 11.6 months (95% CI 14.18-59.82). No significant difference was found in overall survival (OS) between the groups (p = 0.612).
CONCLUSION: For ABC patients, no significant difference in median OS was found between the early use and delayed use of vinorelbine-based regimens, but the short-term efficacy and PFS of vinorelbine-based regimens were significantly better in the early use group than in the delayed use group.

Wang H, Li W, Lai B, et al.
Role of 3' repressor sequences of p53 in anti-cancer drug sensitivity of human lung tumor cells.
Gene. 2016; 594(2):190-196 [PubMed] Related Publications
INTRODUCTION: The C-terminus of p53 and non-coding mRNAs play critical roles in negative regulation. However, their impact on anti-cancer drug sensitivity remains unclear.
METHODS: In this study, we investigated the effects of p53 deleting these sequences on anti-cancer drug sensitivity by drug sensitivity test, flow cytometry, Agilent mRNA expression microarray detection, transplantation tumor in nude mice.
RESULTS: The results showed that the cell line with p53 deleted the C-terminal sequences (p53(del)) was more sensitive to navelbine (NVB) compared to the cell line that carried the full length p53 (p53(wt)). The p53(del) cells was more sensitive to cisplatin (PDD) and 5-fluorouracil (5FU) than p53(wt) cells but there was not significant difference. NVB treatment led to significant G2 arrest and apoptosis in p53(del) cells but not in p53(wt) cells. mRNA expression profile of p53(del) cells indicated that approximately 11% of the 41,000 genes in genome showed differential expression after NVB treatment, among which 2064 genes were up-regulated and 2784 were down-regulated with fold change >2 (P<0.01). Tumor transplantation assay in nude mice showed that the p53 truncation significantly increased tumor sensitivity to NVB compared to the full-length p53, with 99.46% tumor inhibition.
CONCLUSIONS: In summary, deletion of 37 amino acid residues (356-393) and 3' non-coding mRNAs at the C-terminus of p53 selectively increased tumor sensitivity to the mitotic inhibitor NVB.

Huber JM, Amann A, Koeck S, et al.
Evaluation of assays for drug efficacy in a three-dimensional model of the lung.
J Cancer Res Clin Oncol. 2016; 142(9):1955-66 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The focus of the outlined work is the establishment of a three-dimensional lung model for various drug-screening applications.
METHODS: The non-small cell lung cancer (NSCLC) cell line Colo699 was cultivated as monolayer (2D) on plates for 5 days or as microtissues (3D) using a hanging-drop system for 5 and 10 days. Cells and microtissues were treated with afatinib (10-80 µM), cisplatin (100-800 µM) or vinorelbine (25-200 µM) for 24 or 48 hours (h). Cell proliferation and viability were analysed by intra-cellular adenosine triphosphate (ATP) and lactate dehydrogenase release (LDH) assays, annexin V/propidium iodide (PI) staining, and cell cycle determination. Microtissue morphology and size, as well as cell death were evaluated via phase contrast microscopy.
RESULTS: Our results demonstrate the valid determination of viability and cell death using established assays in the 3D system for drug testing. The comparison of ATP, LDH and cytometry data showed moderate (0.40) to very strong (0.99) correlations. Thereby, we observed partially significant differences in drug efficacy between microtissues and 2D cultures dependent from the applied treatment and read-out method. Altogether, microtissues developed resistance to cisplatin and vinorelbine; but remained more vulnerable to afatinib. These findings were confirmed with microscopy.
CONCLUSION: In summary, we established an NSCLC 3D test system with multiple assays compatible for drug-testing applications of substances with different mechanisms of action. In addition, our data support the usage of microtissues as more accurate tools for drug-efficacy testing with the possibility of long-term cultivation and treatment.

McKim A, Walter AC, Sheely KM, et al.
An economic analysis of cisplatin alone versus cisplatin doublets in the treatment of women with advanced or recurrent cervical cancer.
Eur J Gynaecol Oncol. 2016; 37(3):353-6 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: Randomized trials have demonstrated improvements in overall survival when using platinum doublets com- pared to single agent platinum in the treatment of women with advanced or recurrent cervical cancer. The authors sought to evaluate the cost effectiveness of these regimens.
METHODS: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 179 and 204. Cisplatin alone was compared to cisplatin/paclitaxel (CP), cisplatin/topotecan (CT), cisplatin/gemcitabine (GC), cisplatin/vinorelbine (CV), and a hypothetical novel agent. Parameters included overall survival (OS), cost, and complications. One way sensitivity analyses were performed. In further sensitivity analysis, a hypothetical agent that added 3.7 months survival to CP's survival was studied.
RESULTS: The chemotherapy drug costs for six cycles of cisplatin was 89 USD while for cisplatin/paclitaxel it was 489 USD. The highest chemotherapy cost was for GC at 18,306 USD. The average total cost of six cycles CP was 13,250 USD while the average cost of cisplatin alone was 14,573 USD. The highest average cost for six cycles was for GC at 33,559 USD. With cisplatin/paclitaxel being the most effective, the cost effectiveness analysis showed that cisplatin, CT, GC, and VC were all dominated by CP. Because of the regimens being dominated, no baseline ICERs compared to CP were calculable. Sensitivity analyses demonstrate that even all of the chemotherapies were given for free, CP would still be the regimen of choice.
CONCLUSIONS: In this model, CP is the most cost effective regimen for the treatment of these patients with an average cost of 13,250 USD. With the fact that GOG 204 also showed statistically significantly improved survival for CP, CP should be considered the regimen of choice.

Chen XL, Du F, Hong RX, et al.
Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative, metastatic breast cancer.
Chin J Cancer. 2016; 35:39 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Both hormonal therapy (HT) and maintenance capecitabine monotherapy (MCT) have been shown to extend time to progression (TTP) in patients with metastatic breast cancer (MBC) after failure of taxanes and anthracycline-containing regimens. However, no clinical trials have directly compared the efficacy of MCT and HT after response to first-line capecitabine-based combination chemotherapy (FCCT) in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
METHODS: We retrospectively analyzed the charts of 138 HR-positive and HER2-negative MBC patients who were in non-progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, in Beijing, China. The median number of first-line chemotherapy cycles was 6 (range, 4-8); combined agents included taxanes, vinorelbine, or gemcitabine. Of these 138 patients, 79 received MCT, and 59 received HT. Single-agent capecitabine was administered at a dose of 1250 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, repeated every 3 weeks. Of the 59 patients who received HT, 37 received aromatase inhibitors (AIs), 8 received selective estrogen receptor modulators (SERMs), and 14 received goserelin plus either AIs or SERMs. We then compared the MCT group and HT group in terms of treatment efficacy.
RESULTS: With a median follow-up of 43 months, patients in the HT group had a much longer TTP than patients in the MCT group (13 vs. 8 months, P = 0.011). When TTP was adjusted for age, menopausal status, Karnofsky performance status score, disease-free survival, site of metastasis, number of metastatic sites, and response status after FCCT, extended TTP was still observed for patients in the HT group (hazard ratio: 0.63; 95% confidence interval: 0.44-0.93; P = 0.020). We also observed a trend of overall survival advantage for patients in the HT group vs. patients in the MCT group, but the difference was not significant (43 vs. 37 months, P = 0.400). In addition, patients in the HT group generally tolerated the treatment well, whereas patients in the MCT group experienced grades 3-4 adverse events, the most frequent of which were hand-foot syndrome (15.8%) and hematologic abnormalities (7.6%).
CONCLUSION: For HR-positive and HER2-negative MBC patients, HT might be considered a treatment after response to FCCT but prior to MCT as a long-term administration.

Elharrar X, Barbolosi D, Ciccolini J, et al.
A phase Ia/Ib clinical trial of metronomic chemotherapy based on a mathematical model of oral vinorelbine in metastatic non-small cell lung cancer and malignant pleural mesothelioma: rationale and study protocol.
BMC Cancer. 2016; 16:278 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Metronomic oral vinorelbine is effective in metastatic NSCLC and malignant pleural mesothelioma, but all the studies published thus far were based upon a variety of empirical and possibly suboptimal schedules, with inconsistent results. Mathematical modelling showed by simulation that a new metronomic protocol could lead to a better safety and efficacy profile.
DESIGN: This phase Ia/Ib trial was designed to confirm safety (phase Ia) and evaluate efficacy (phase Ib) of a new metronomic oral vinorelbine schedule. Patients with metastatic NSCLC or malignant pleural mesothelioma in whom standard treatments failed and who exhibited ECOG performance status 0-2 and adequate organ function will be eligible. Our mathematical PK-PD model suggested an alternative weekly D1, D2 and D4 schedule (named Vinorelbine Theoretical Protocol) with a respective dose of 60, 30 and 60 mg. Trial recruitment will be two-staged, as 12 patients are planned to participate in phase Ia to confirm safety and consolidate the calibration of the model parameters. Depending on the phase Ia results and after a favourable decision from a consultative committee, the extension phase (phase Ib) will be an efficacy study including 20 patients who will receive the Optimal Vinorelbine Theoretical Protocol. The primary endpoint is the tolerance (assessed by CTC v4.0) for the phase Ia and the objective response according to RECIST 1.1 for phase Ib. An ancillary study on circulating angiogenesis biomarkers will be a subproject of the trial.
DISCUSSION: This ongoing trial is the first to prospectively test a mathematically optimized schedule in metronomic chemotherapy. As such, this trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in patients with cancer.
TRIAL REGISTRATION: EudraCT N°: 2015-000138-31.

Farhat F, Kattan JG, Ghosn M
Oral vinorelbine in combination with trastuzumab as a first-line therapy of metastatic or locally advanced HER2-positive breast cancer.
Cancer Chemother Pharmacol. 2016; 77(5):1069-77 [PubMed] Related Publications
PURPOSE: Vinorelbine-trastuzumab combination proved to be an effective first-line treatment for patients with locally advanced or metastatic breast cancer (MBC). Oral chemotherapy represents a step forward in MBC management. To improve patients' comfort using the oral form of vinorelbine, we conducted a multicenter phase II study to investigate the efficacy and safety of the oral vinorelbine-trastuzumab combination in women with MBC with human epidermal growth factor receptor 2 (HER2) overexpression.
METHODS: Main eligibility criteria: HER2-positive disease, no adjuvant chemotherapy within the last 6 months and no prior chemotherapy for MBC. Patients were treated with oral vinorelbine 80 mg/m(2) D1, D8, D15 (following first 3 administrations at 60 mg/m(2) during the first cycle) for a total of 8 cycles (1 cycle = 3 weeks), in combination with trastuzumab 6 mg/kg on D1 (loading dose: 8 mg/kg) every 3 weeks or 4 mg/kg (loading dose: 6 mg/kg) weekly. Response was evaluated every 2 cycles using RECIST 1.0.
PRIMARY ENDPOINT: objective response rate (ORR); secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: In the full population (n = 26), median age was 50.7 years and median WHO PS 0. Median disease-free interval was 50.7 months [95 % CI (43.6-57.9)]. In the evaluable patients population, ORR was 56 % [95 % CI (34.9-75.6)], including 3 complete responses (12 %) and 11 partial (44 %); 8 (32 %) patients had stable disease resulting in a clinical benefit (or disease control) rate of 88 % [95 % CI (68.8-97.5)]. Median DOR was 7.1 months [95 % CI (3.9-10.2)], median PFS 6.7 months (95 % CI 3.5-10), and median OS 27.9 months (95 % CI 17.4-38.3). Treatment was generally well tolerated with main observed grade 3/4 hematological toxicities being neutropenia (46 %) and anemia (4 %). Grade 3-4 nausea-vomiting were observed in 11.5 % of patients.
CONCLUSIONS: Our results confirm the efficacy of oral vinorelbine-trastuzumab combination as a first-line treatment in HER2-positive locally advanced or MBC patients with an acceptable safety profile. Oral vinorelbine-trastuzumab optimizes the convenience of this chemotherapy regimen, especially for patients receiving trastuzumab every 3 weeks.

Vecchione L, Gambino V, Raaijmakers J, et al.
A Vulnerability of a Subset of Colon Cancers with Potential Clinical Utility.
Cell. 2016; 165(2):317-30 [PubMed] Related Publications
BRAF(V600E) mutant colon cancers (CCs) have a characteristic gene expression signature that is also found in some tumors lacking this mutation. Collectively, they are referred to as "BRAF-like" tumors and represent some 20% of CCs. We used a shRNA-based genetic screen focused on genes upregulated in BRAF(V600E) CCs to identify vulnerabilities of this tumor subtype that might be exploited therapeutically. Here, we identify RANBP2 (also known as NUP358) as essential for survival of BRAF-like, but not for non-BRAF-like, CC cells. Suppression of RANBP2 results in mitotic defects only in BRAF-like CC cells, leading to cell death. Mechanistically, RANBP2 silencing reduces microtubule outgrowth from the kinetochores, thereby inducing spindle perturbations, providing an explanation for the observed mitotic defects. We find that BRAF-like CCs display far greater sensitivity to the microtubule poison vinorelbine both in vitro and in vivo, suggesting that vinorelbine is a potential tailored treatment for BRAF-like CCs.

Zhao HY, Zhou HY, Wang YT, et al.
Assessment on the Efficacy and Safety of Aidi Injection Combined with Vinorelbine and Cisplatin for Treatment of Advanced Nonsmall Cell Lung Cancer.
Chin Med J (Engl). 2016; 129(6):723-30 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).
METHODS: Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.
RESULTS: Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m 2 , combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05-1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30-0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m 2 , no significant differences in efficiency (RR = 1.11, 95% CI [0.87-1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71-1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia.
CONCLUSIONS: Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.

Bakirhan K, Sharma J, Perez-Soler R, Cheng H
Medical Treatment in Elderly Patients with Non-Small Cell Lung Cancer.
Curr Treat Options Oncol. 2016; 17(3):13 [PubMed] Related Publications
OPINION STATEMENT: Lung cancer is the leading cause of cancer-related deaths worldwide. In the USA, ≈60 % of lung cancer cases are diagnosed in elderly patients (≥65 years of age). However, elderly patients are underrepresented in clinical studies, leading to a paucity of evidence to guide treatment decisions. Several treatment barriers exist in elderly patients, including comorbidities and poor performance status. In addition, lack of reliable geriatric assessment tools and physician reluctance to treat may contribute to undertreatment in this population. For decades, systemic chemotherapy for elderly patients with advanced non-small cell lung cancer (NSCLC) was either omitted or given as monotherapy, frequently with significant dose reductions, potentially compromising the efficacy of these therapies. Recent analyses of elderly subgroups from multiple clinical trials provide evidence for improved outcomes associated with platinum-based doublet chemotherapies vs monotherapy. Moreover, in the new era of precision medicine, molecularly targeted therapies and more recently immune-targeting therapies (anti-PD-1 and anti-PD-L1 agents) exhibit relatively milder toxicities but superior clinical outcomes in subgroups of patients compared with conventional cytotoxic chemotherapies. Further clinical trials will be needed to confirm similar safety and efficacy profiles of these therapeutic approaches in the elderly compared with their younger counterparts. In this article, we review available evidence from clinical studies and also present expert consensus on the management of NSCLC in the elderly, including treatment in the adjuvant setting and treatment of advanced disease. Screening tools, such as the Comprehensive Geriatric Assessment, that help to identify the right population of elderly patients suitable for systemic treatment are also discussed.

Welt A, Marschner N, Lerchenmueller C, et al.
Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial.
Breast Cancer Res Treat. 2016; 156(1):97-107 [PubMed] Free Access to Full Article Related Publications
The study was designed to evaluate efficacy and superiority of capecitabine/bevacizumab + vinorelbine (CAP/BEV/VIN) compared to CAP/BEV alone. Main purpose was to introduce a taxane-/anthracycline-free first-line treatment in advanced breast cancer (ABC), in order to avoid long-term toxicities. In this open-label, superiority, phase 3 trial, patients with HER2-negative ABC were randomized 1:1 to receive either oral CAP at 1000 mg/m(2) [twice daily, days 1-14, q3w] plus intravenous BEV at 15 mg/kg [day 1, q3w] (arm A) or in addition to this protocol intravenous VIN at 25 mg/m(2) [days 1 + 8, q3w] (arm B) until disease progression, unacceptable toxicity or withdrawal of consent. Between 26 February 2009 and 26 October 2012, we randomised 600 patients (arm A N = 300; arm B N = 300) from 57 German outpatient-centres and 2 university hospitals. Median progression-free survival (PFS) (primary endpoint) was not improved with VIN (CAP/BEV, 8.8 months; CAP/BEV/VIN, 9.6 months; HR 0.84 [95 % CI 0.70-1.01], P = 0.058). Median overall survival (OS) (secondary endpoint) was 25.1 and 27.2 months for CAP/BEV and CAP/BEV/VIN, respectively, average HR 0.85 [95 % CI 0.70-1.03], P = 0.104). The 1- and 2-year OS rates appeared to be similar (78.0 and 77.0 %; 53.0 and 54.0 %). Toxicity profiles were generally mild and manageable. Adverse events occurred more frequently in arm B. Regarding the balance between clinical efficacy (PFS, OS) and toxicity, the CAP/BEV combination provides a favourable treatment option in first-line ABC avoiding taxane- and/or anthracycline-induced long-term toxicity. Superiority of CAP/BEV/VIN was not met, and side effects were even enhanced. Nevertheless, no safety issues occurred.

Polat G, Yılmaz U, Anar C, et al.
Is there relationship between excision repair cross-complementation 1 expression level and response to treatment and prognosis in an advanced stage lung cancer treated with cisplatin-based chemotherapy?
Indian J Cancer. 2015 Jul-Sep; 52(3):277-80 [PubMed] Related Publications
AIM: It is important to know the tumor resistance against cisplatin before the treatment of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the response to treatment and survival in patients with NSCLC treated with cisplatin-based chemotherapy according to excision repair cross-complementation 1 (ERCC1) expression.
MATERIALS AND METHODS: Among 119 patients treated with cisplatin and vinorelbine or docetaxel, 39 (32%) patients enrolled who have enough tumor tissue to analyze ERCC1 expression. ERCC1 expression defined as negative in score 0-1, positive in score 2-3.
RESULTS: There was no difference between ERCC1 positive and negative groups (P = 0.63). Mean survival was 14.7 months (95% confidence interval [CI]; 10.0-19.3 month) in ERCC1 negative group, 10.9 months (95% CI; 7.4-14.3 month) in ERCC1 positive group (P = 0.23). Progression free survival was 7.9 months in ERCC1 negative group (95% CI; 5.8-9.9 months), 6.2 months in ERCC1 positive group (95% CI; 4.0-8.5 months) (P = 0.27).
CONCLUSION: Identification of ERCC1 expression level of tumor tissues in NSCLC patients before treatment was not useful in prediction of treatment response and prognosis.

Thallinger C, Lang I, Kuhar CG, et al.
Phase II study on the efficacy and safety of Lapatinib administered beyond disease progression and combined with vinorelbine in HER-2/neu- positive advanced breast cancer: results of the CECOG LaVie trial.
BMC Cancer. 2016; 16:121 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Vinorelbine constitutes effective chemotherapy for metastatic breast cancer (MBC) and acts synergistically with trastuzumab in HER-2/neu positive disease. The present study was set out to evaluate the efficacy and safety of vinorelbine when combined with lapatinib, an anti-HER2 tyrosine-kinase inhibitor, as late-line regimen administered beyond previous disease progression on prior lapatinib in patients with HER-2/neu- positive MBC.
METHODS: The CECOG LaVie study was designed as open-labeled, single-arm, multicenter phase II trial. Patients had to be pretreated with lapatinib plus chemotherapy, and received lapatinib at a daily dose of 1250 mg in combination with vinorelbine 20 mg/m(2) i.v. on days 1 and 8 of a three-week cycle until disease progression, intolerable toxicity or withdrawal of consent. Progression-free survival (PFS) was defined as primary study endpoint; secondary endpoints included overall survival (OS), response rate according to RECIST 1.1, and safety. The study was terminated early due to poor accrual.
RESULTS: A total number of nine patients were included; lapatinib administered beyond disease progression combined with vinorelbine resulted in a median PFS of 7.7 months (95% CI 0.56-14.91) and a median OS of 23.4 months (95% CI 16.61-30.13), respectively. Partial remission was seen in one of nine patients, three patients had stable disease of > six months, whereas the remaining five patients had primary disease progression. In two patients, modification of vinorelbine dose due to toxicity became necessary; no dose modification was needed for lapatinib. The majority of reported adverse events (AE) were grade 1 and 2 in severity with diarrhea being the most commonly observed AE CONCLUSION: In this heavily pretreated patient population, combination of vinorelbine plus lapatinib showed encouraging activity and was characterized by an acceptable safety profile. Despite the low patient number, lapatinib plus vinorelbine may constitute a potential treatment option in heavily pretreated patients with HER-2/neu-positive MBC previously exposed to lapatinib.
TRIAL REGISTRATION: EudraCT number 2009-016826-15, (15. 10.2009).

Harbeck N, Huang CS, Hurvitz S, et al.
Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial.
Lancet Oncol. 2016; 17(3):357-66 [PubMed] Related Publications
BACKGROUND: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer.
METHODS: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m(2) per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566.
FINDINGS: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none).
INTERPRETATION: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab.
FUNDING: Boehringer Ingelheim.

Heo SJ, Jung I, Lee CK, et al.
A randomized phase II trial of ERCC1 and RRM1 mRNA expression-based chemotherapy versus docetaxel/carboplatin in advanced non-small cell lung cancer.
Cancer Chemother Pharmacol. 2016; 77(3):539-48 [PubMed] Related Publications
OBJECTIVES: To evaluate whether the selection of first-line chemotherapy based on ERCC1 and RRM1 mRNA expression levels would improve clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients.
MATERIALS AND METHODS: Eligible patients were randomly assigned 1:1 to the experimental and control arms; the experimental arm received gemcitabine/carboplatin (GC) if ERCC1 and RRM1 expression was low, gemcitabine/vinorelbine (GV) if ERCC1 was high and RRM1 was low, docetaxel/carboplatin (DC) if ERCC1 was low and RRM1 was high, and docetaxel/vinorelbine (DV) if both were high. In the control arm, patients received DC.
RESULTS: This study was prematurely terminated after the futility analysis of 43 progression-free survival (PFS) events. A total of 55 patients (n = 26 in the experimental arm, n = 29 in the control arm) were evaluable for efficacy and toxicity. Nineteen (73.1%) patients were assigned to receive GC, 0 (0.0%) to GV, 4 (15.4%) to DC, and 3 (11.5%) to DV in the experimental arm. The overall response rates were 42.3 and 48.3% in the experimental and control arms, respectively, which were not statistically different (P = 0.657). The median PFS was 5.2 months in the experimental arm and 5.4 months in the control arm (P = 0.286). The median overall survival was 17.4 months in the experimental arm and 12.6 months in the control arm (P = 0.638). The occurrence of grade 3 or higher neutropenia (69.2 vs. 93.1%, P = 0.035) and febrile neutropenia (3.8 vs. 24.1%, P = 0.054) was more common in the control arm.
CONCLUSION: ERCC1 and RRM1 mRNA expression-based chemotherapy did not improve clinical outcomes in advanced NSCLC (NCT01648517).

Flentje M, Huber RM, Engel-Riedel W, et al.
GILT--A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer.
Strahlenther Onkol. 2016; 192(4):216-22 [PubMed] Related Publications
BACKGROUND: Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin.
METHODS: Patients received two cycles of oral vinorelbine (50 mg/m(2) days 1, 8 and 15) + cisplatin (20 mg/m(2) days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m(2) days 1 and 8) + cisplatin (80 mg/m(2) day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS).
RESULTS: A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively.
DISCUSSION: Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC.

Kotecki N, Hiret S, Etienne PL, et al.
First-Line Chemotherapy for Metastatic Esophageal Squamous Cell Carcinoma: Clinico-Biological Predictors of Disease Control.
Oncology. 2016; 90(2):88-96 [PubMed] Related Publications
OBJECTIVE: This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy.
METHODS: A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients.
RESULTS: Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC.
CONCLUSION: We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.

Xu M, Jiang D, Shen J, et al.
Distinct characterization of two vinorelbine-resistant breast cancer cell lines developed by different strategies.
Oncol Rep. 2016; 35(4):2355-63 [PubMed] Related Publications
Resistance to chemotherapy is a major obstacle to the successful treatment of breast cancer patients. Recently, we successfully established two vinorelbine-resistant sublines, BC-DS and BC-TS, from the human breast cancer cell line BCap37, with different 'two-stage screening methods'. Interestingly, though BC-DS and BC-TS were developed from the same BCap37 cell line with the same drug, they showed remarkable differences. Compared with the parental BCap37 cells both BC-DS and BC-TS had resistance to vinorelbine, but the resistant characterizations are both unstable. BC-DS showed increased migration capability while BC-TS showed reduced migration capability. When investigating their multidrug resistance, we found BC-DS became more sensitive to methotrexate, which suggested that combination of MTX and vinorelbine could be a new treatment strategy. Moreover, BC-DS and BC-TS overexpressed P-glycoprotein at different levels. Our research also showed that the present clinical usage of vinorelbine is reasonable. These findings suggest that the vinorelbine-induced multiple drug resistance (MDR) sublines may be used as an in vitro model not only to further elucidate possible mechanisms of MDR involved in the human breast cancer, but also to find methods to optimize the curative effect of vinorelbine in clinic.

Smit E, Moro-Sibilot D, Carpeño Jde C, et al.
Cisplatin and carboplatin-based chemotherapy in the first-line treatment of non-small cell lung cancer: Analysis from the European FRAME study.
Lung Cancer. 2016; 92:35-40 [PubMed] Related Publications
OBJECTIVES: To explore patient and disease factors, and reasons behind the physician's choice of platinum backbone for the first-line treatment of non-small cell lung cancer (NSCLC), as observed in a European prospective observational study of patients receiving platinum-based chemotherapy as first-line treatment for advanced or metastatic NSCLC (the FRAME study). Additionally, overall survival (OS) for patients who received cisplatin or carboplatin was evaluated.
MATERIALS AND METHODS: A post-hoc analysis of the prospective study population was conducted. Baseline characteristics of patients receiving cisplatin versus carboplatin were compared and summarized by propensity score. Survival for matched patients was summarized using the Kaplan-Meier approach.
RESULTS: Of the 1564 patients who were included in the prospective study, 1520 received either cisplatin (54%) or carboplatin (46%) in combination with pemetrexed, gemcitabine, taxanes or vinorelbine. Patients treated with carboplatin were older than patients receiving cisplatin (mean age 67 versus 61 years; p<0.001), had poorer performance status (p<0.001), and more comorbidities (p<0.001). Cisplatin was most frequently combined with pemetrexed (47%), and carboplatin most frequently with taxanes (31%). Unadjusted median OS estimates for patients from the total prospective study sample were 11.5 months (95% confidence interval [CI] 10.1-12.9) for cisplatin recipients and 9.0 months (95% CI 8.1-10.6) for carboplatin recipients. Median (95% CI) overall survival for the matched cohorts was 10.8 months (8.8-14.3) for cisplatin versus 9.5 months (8.2-11.3) for carboplatin; p=0.086.
CONCLUSION: This post-hoc analysis illustrated real-life differences in patients with NSCLC prescribed platinum-based first-line treatment, and suggested that baseline patient and disease characteristics were associated with physician's choice of platinum agent, with cisplatin being more frequently prescribed to younger and fitter patients.

Kreuter M, Vansteenkiste J, Fischer JR, et al.
Three-Year Follow-Up of a Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin and Vinorelbine (the TREAT Study).
J Thorac Oncol. 2016; 11(1):85-93 [PubMed] Related Publications
INTRODUCTION: Adjuvant chemotherapy in non-small cell lung cancer (NSCLC) improves survival but is associated with significant toxicity. The Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin and Vinorelbine (TREAT study) was designed to test the hypothesis that a protocol with reduced toxicity might improve feasibility of postoperative delivery of adjuvant chemotherapy drugs to patients with NSCLC, thereby improving compliance and, potentially, survival.
METHODS: Two adjuvant regimens were evaluated for feasibility in 132 patients with NSCLC: the standard regimen of cisplatin and vinorelbine (CVb) (cisplatin 50 mg/m(2) on day 1 and day 8 and vinorelbine 25 mg/m(2) on days 1, 8, 15, and 22 every 4 weeks) and a regimen consisting of cisplatin and pemetrexed (CPx) (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 every 3 weeks). The primary end-point analysis showing that CPx is safe and feasible with dose delivery superior to that of CVb has already been published. Here we report the 3-year follow-up results of the secondary efficacy end points-overall, relapse-free, distant metastasis-free, and local relapse-free survival-also with regard to histologic diagnosis.
RESULTS: After a median of 39 months, no significant differences in any of the outcome parameters between CVb and CPx were observed. Also, histologic diagnosis and tumor size in stage IB did not influence survival in the CPx-treated patients. Yet, Cox regression analyses showed that overall survival at 3 years was significantly correlated with feasibility and the occurrence of dose-limiting toxicity.
CONCLUSIONS: Although adjuvant chemotherapy with CPx is safe and characterized by less toxicity and better dose delivery than CVb, overall survival was not influenced by treatment arm in the context of this phase II trial.

Zhao Q, Wang Z, Huang W, et al.
Phase III study of cisplatin with pemtrexed or vinorelbine plus concurrent late course accelerated hyperfractionated radiotherapy in patients with unresectable stage III non-small cell lung cancer.
Oncotarget. 2016; 7(7):8422-31 [PubMed] Free Access to Full Article Related Publications
Our aim was to evaluate the efficacy and safety of cisplatin with pemtrexed or vinorelbine and concurrent late course accelerated hyperfractionated radiotherapy (LCAHRT). Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to two regimens. The experimental (PP) arm included cisplatin, pemtrexed and concurrent LCAHRT based on bilateral lung V20 = 33%. The control (NP) arm used cisplatin, vinorelbine with the same radiotherapy protocol. The primary endpoint was overall survival. Median survival times were 26.0 months (95% CI 23.2 to 28.7 months) and 28.5 months (95% CI 17.1 to 39.9 months) for the NP and PP arms, respectively (P = 0.26). Median progression-free survival was 12.5 months and 17.5 months in the NP and PP arms (P = 0.07). In both arms of the study, there were no differences in overall survival between patients with squamous and nonsquamous NSCLC. The incidences of grade 3 or 4 toxicity were higher in NP than PP arm. With concurrent LCAHRT, pemetrexed/cisplatin was equally as efficacious as vinorelbine/cisplatin, but showed a more favorable toxicity profile.

Barth C, Naveau L, Touboul E, et al.
Efficacy and safety of vinorelbine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma patients.
Anticancer Drugs. 2016; 27(4):349-52 [PubMed] Related Publications
The aim of this study was to evaluate the efficacy and tolerance of vinorelbine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral or intravenous vinorelbine according to the pluridisciplinary tumor board's decision. Efficacy and safety outcomes were analyzed retrospectively. Twenty-three patients were included in the study. Sixteen patients (69%) had received at least two previous lines of chemotherapy. The disease control rate was 19%. The median progression-free survival was 2.6 months and the median overall survival was 3.4 months. The rate of grade 3-4 side effects was low (13%). Only one patient discontinued treatment because of side effects. Vinorelbine seems to be a well-tolerated regimen in heavily pretreated patients. However, this regimen does not seem to be efficient enough to be recommended.

Jeannin G, Merle P, Janicot H, et al.
Combined treatment modalities in Pancoast tumor: results of a monocentric retrospective study.
Chin Clin Oncol. 2015; 4(4):39 [PubMed] Related Publications
BACKGROUND: A retrospective monocentric study of consecutive patients with superior sulcus tumor non-small cell lung cancer (SS-NSCLC), treated by induction concurrent chemoradiotherapy (CRT), article management.
METHODS: From 1994 to 2005, 36 patients (15 T3, 21 T4 tumors, including N2-N3 node involvement) received induction CRT with cisplatin/vinorelbine/fluorouracil combined with 44 Gy radiotherapy (5 daily 2 Gy fractions/week). After CRT completion, RECIST evaluation and operability were assessed. In resectable patients, surgery was performed one month after CRT. Patients with unresectable disease followed CRT up to 66 Gy. The median of follow-up period was 38.6 months [2-206].
RESULTS: Induction CRT was completed for 94.4% with 71% radiological objective response (OR). Sixteen patients (44%) underwent surgical resection, and pathologic complete resection was performed in 93.8%. There were 7 patients (44%) with pathologic complete response. The median disease-free survival (DFS) time was 12.9 months with DFS rates at 1 and 2 years 53.6% and 39.1% respectively. The median overall survival (OS) was 46.4 months. The OS rates at 2 and 5 years were 68.8% and 37.5% respectively with no difference between T3 and T4 tumors. In unresectable disease, the median DFS time was 8.1 months. The DFS rate at 1 year was 25.2%. The median OS was 9.1 months. The OS rates at 1 and 2 years were 45% and 16.9% respectively. Recurrences were found in 72% of patients. Brain metastasis was the most common site of recurrence. Prognostic factors for OS were the response to induction treatment, the possibility of surgery, and pathologic complete response.
CONCLUSIONS: This trimodality treatment regimen confers a survival outcome in agreement with previous studies. Patients with pretreatment N3 lymph node should be included in trimodality treatment.

Chaft JE, Dunphy M, Naidoo J, et al.
Adaptive Neoadjuvant Chemotherapy Guided by (18)F-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial.
J Thorac Oncol. 2016; 11(4):537-44 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
INTRODUCTION: Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and an opportunity to switch treatment regimens. Response measured by fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) correlates with clinical outcomes better than computed tomography (CT) does. This trial assessed PET-measured response rate to alternative chemotherapy in patients with a suboptimal PET response after two cycles of neoadjuvant chemotherapy.
METHODS: This phase II study enrolled patients with resectable stage IB-IIIA lung cancers (primary tumor ≥ 2 cm and peak standard uptake value [SUVpeak] ≥ 4.5). Patients had a pretreatment (18)F-FDG PET/CT scan before two cycles of cisplatin (or carboplatin) plus gemcitabine (squamous cell carcinoma) or pemetrexed (adenocarcinoma) and then a repeat PET/CT scan. If SUVpeak in the primary tumor decreased by at least 35%, patients continued the initial chemotherapy. Individuals with less than a 35% PET response were switched to vinorelbine plus docetaxel. Postoperative radiotherapy was recommended to all patients with positive N2 nodes. A Simon's optimal two-stage design was used to evaluate the primary end point of a PET Response in Solid Tumors-defined response rate to vinorelbine plus docetaxel in previously nonresponding patients.
RESULTS: Forty patients were enrolled. Fifteen patients (38% [95% confidence interval: 38-53]) had less than a 35% decrease in SUVpeak, and 13 received vinorelbine plus docetaxel. The study met its primary end point with 10 of 15 PET metabolic responses to alternate therapy (67%). Chemotherapy toxicities never precluded surgical exploration.
CONCLUSIONS: Utilizing (18)F-FDG PET/CT to assess response and change preoperative chemotherapy in nonresponding patients can improve radiographic measures of response. This adaptive approach can also be used to test new drugs, attempting to optimize perioperative chemotherapy to achieve better long-term outcomes.

Launay S, Sabatier R, Brunelle S, et al.
METRO1: A Phase I Study of Metronomic Chemotherapy in Adults with Advanced Refractory Solid Tumors.
Anticancer Res. 2016; 36(1):293-9 [PubMed] Related Publications
BACKGROUND: The present monocentric and prospective phase 1 study evaluated the safety of a metronomic chemotherapy in refractory tumors.
PATIENTS AND METHODS: Patients with advanced solid cancer refractory to standard therapy received a combination of low-dose vinorelbine, cyclophosphamide and interferon-alpha. A dose escalation model with 3 levels was planned. The primary end-point was safety and tolerability, secondary end-points were treatment continuation rate at 4 months, progression-free survival (PFS), overall survival (OS), radiological assessment (MRI) of anti-angiogenic effect.
RESULTS: Thirty patients were enrolled. No dose-limiting toxicity was observed. All but two adverse events were toxicities of grade 1-2. Treatment continuation rate at 4 months was 6.67% (2 out of 30 patients). Median PFS and OS were 1.6 and 6.1 months. Exploratory MRI analyses related to anti-angiogenic effect did not show any relevant modification.
CONCLUSION: This combination of metronomic chemotherapy is well-tolerated and deserves to be deeply explored in refractory solid tumors.

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