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Cisplatin

"An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle." (MeSH 2013)

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Latest Research Publications

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Yu N, Xiong Y, Wang C
Bu-Zhong-Yi-Qi Decoction, the Water Extract of Chinese Traditional Herbal Medicine, Enhances Cisplatin Cytotoxicity in A549/DDP Cells through Induction of Apoptosis and Autophagy.
Biomed Res Int. 2017; 2017:3692797 [PubMed] Free Access to Full Article Related Publications
Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects. Cotreatment with BZYQD and cisplatin induced intrinsic apoptotic pathways which were measured by condensed nuclear chromatin, Annexin V/PI apoptosis assay, and apoptosis related proteins expression. In addition, cotreatment with BZYQD and cisplatin also activated autophagy, as indicated by an increase in LC3 puncta, classical autophagosomes and/or autolysosomes, and an accumulation of LC3-II and ATG7 protein. Finally, cotreatment with BZYQD and cisplatin resulted in the generation of ROS and scavenging ROS by NAC almost completely suppressing cell death. These results suggest that cotreatment with BZYQD and cisplatin might reverse cisplatin resistance by inducing ROS accumulation, which activates apoptosis and autophagy by oxidative stress. The combination of BZYQD and cisplatin may represent a novel approach in treatment for NSCLC and thus offer a new target for chemotherapy.

Li C, Ge X, Wang L
Construction and comparison of different nanocarriers for co-delivery of cisplatin and curcumin: A synergistic combination nanotherapy for cervical cancer.
Biomed Pharmacother. 2017; 86:628-636 [PubMed] Related Publications
PURPOSE: Co-delivery of two or more drugs into the same cancer cells or tissues in the same nanocarriers provides a new paradigm in cancer treatment. In this study, two kinds of nanocarriers: lipid-polymer hybrid nanoparticles (LPNs) and polymeric nanoparticles (PNPs) were constructed and compared for co-delivery of cisplatin (DDP) and curcumin (CUR).
METHODS: DDP and CUR loaded LPNs (D/C/LPNs) and PNPs (D/C/PNPs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), and drug release. Their in vitro cytotoxicity and in vivo anti-tumor efficacy was studied on human cervix adenocarcinoma cell line (HeLa cells) and mice bearing cervical cancer model.
RESULTS: Compared with D/C/PNPs, D/C/LPNs showed significantly higher cytotoxicity in vitro. D/C/LPNs also displayed the best antitumor activity than other formulations tested in vivo.
CONCLUSIONS: The results demonstrated that LPNs could improve the anticancer efficacy of drugs to higher levels than PNPs and free drugs, thus could serve as an effective drug system for targeted and synergistic co-delivery nanomedicine for cervical cancer chemotherapy.

Isaka T, Nakayama H, Yokose T, et al.
Platinum-Based Adjuvant Chemotherapy for Stage II and Stage III Squamous Cell Carcinoma of the Lung.
Ann Thorac Cardiovasc Surg. 2017; 23(1):19-25 [PubMed] Related Publications
INTRODUCTION: The efficacy of platinum-based adjuvant chemotherapy (PBAC) for pathological stage II and stage III squamous cell carcinoma (SCC) of the lung was analyzed retrospectively.
MATERIALS AND METHODS: The prognoses of 94 patients with stage II and stage III SCC with or without PBAC (more than three courses of cisplatin-, carboplatin-, and nedaplatin-based adjuvant chemotherapy) were compared.
RESULTS: The mean observation period was 46.1 months. PBAC was not administered for the following reasons: 39 (55.7%) patients had comorbidities, 25 (35.7%) were older than 75 years, 19 (27.1%) patients underwent surgery before the approval of PBAC, and 3 (4.3%) patients could not continue PBAC (≤2 cycles) because of adverse events. PBAC patients (n = 24) were significantly younger than non-PBAC patients (n = 70; 66.3 vs 69.6 years old, respectively; p = 0.043). Disease-free survival (DFS) did not differ between PBAC and non-PBAC patients (55.0% and 67.1%, respectively; p = 0.266). PBAC patients tended to have worse overall survival (OS) than non-PBAC patients (56.1% and 70.2%, respectively; p = 0.138). PBAC was not prognostic for OS (hazard ratio (HR), 2.11; 95% confidence interval (CI), 0.82%-5.40%; p = 0.120).
CONCLUSION: PBAC did not improve the prognoses of patients with pathological stage II or stage III SCC in the single institution experience.

Lu C, Shan Z, Li C, Yang L
MiR-129 regulates cisplatin-resistance in human gastric cancer cells by targeting P-gp.
Biomed Pharmacother. 2017; 86:450-456 [PubMed] Related Publications
Development of multiple drug resistance (MDR) to chemotherapy is the major reason for the failure of gastric cancer (GC) treatment. P-glycoprotein (P-gp), which is encoded by MDR gene 1, as one of the mechanisms responsible for MDR. Mounting evidence has demonstrated that the drug-induced dysregulation of microRNAs (miRNAs) function may mediate MDR in cancer cells. However, the underling mechanisms of miRNA-mediated MDR in GC remain unclear. Here, we found that miR-129 was downregulated in cisplatin-resistant GC tissues/cells. Our results also showed that overexpression of miR-129 decreased cisplatin-resistance in cisplatin-resistant GC cells, and miR-129 knockdown reduced chemosensitivity to cisplatin in cisplatin-sensitive GC cells. Furthermore, miR-129 activated the intrinsic apoptotic pathway via upregulating caspase-9 and caspase-3. Most importantly, we further confirmed that P-gp is the functional target of miR-129 by regulating cisplatin-resistance in GC cells. These results suggested that miR-129 reversed cisplatin-resistance through inhibiting the P-gp expression in GC cells.

Cho O, Noh OK, Oh YT, et al.
Clinical Impact of Escalating Relative High-dose-rate Intracavitary Brachytherapy Dose in Stage IIB Cervical Cancer.
Anticancer Res. 2017; 37(1):327-334 [PubMed] Related Publications
BACKGROUND/AIM: To investigate whether high-dose-rate (HDR) intracavitary brachytherapy (IBT) dose ratios can predict treatment outcomes in patients with stage IIB cervical cancer.
PATIENTS AND METHODS: Ninety-three patients treated with weekly cisplatin-based concurrent chemoradiotherapy and HDR IBT were analyzed. Potential prognostic factors and treatment outcomes were compared between low-HDR-IBT-ratio (≤0.43) and high-HDR-IBT-ratio (>0.43) groups, and univariate and multivariate analyses were performed.
RESULTS: Five-year disease-specific survival (DSS) and progression-free survival (PFS) rates were significantly shorter in the low-compared to the high-HDR-IBT-ratio group. A high HDR IBT ratio was confirmed as an independent prognostic factor for DSS and PFS.
CONCLUSION: A high HDR IBT dose ratio improves DSS and PFS in patients with stage IIB cervical cancer. Therefore, active administration of HDR IBT beyond previously accepted levels may be necessary for the treatment of locally advanced cervical cancer.

Sugiyama K, Narita Y, Kadowaki S, et al.
Platinum-based Doublet Chemotherapy for Advanced Gastric Cancer with Disseminated Intravascular Coagulation.
Anticancer Res. 2017; 37(1):309-313 [PubMed] Related Publications
BACKGROUND: Disseminated intravascular coagulation (DIC) is a rare complication of advanced gastric cancer (AGC). Despite reports of the efficacy of chemotherapy for AGC with DIC, little is known of platinum-based doublet therapy.
PATIENTS AND METHODS: We conducted a single-institute, retrospective chart review of 500 consecutive chemotherapy-naïve patients with advanced gastric adenocarcinoma (recurrent or metastatic) from November 2010 to November 2015.
RESULTS: Six patients were diagnosed with AGC with DIC (1.2%); five (1.0%; 3 men, 2 women) received platinum-based doublet chemotherapy. All patients exhibited improved DIC and thrombocytopenia and survived for >100 days (range=114-313) with no therapy-related mortality. Grade ≥3 adverse effects included neutropenia, anemia, hyponatremia, catheter-related infection and diarrhea (maximum: 2 patients each).
CONCLUSION: Fluoropyrimidine plus platinum combination therapy was effective against DIC and yielded acceptable survival outcomes. Combination chemotherapy should be considered as a primary therapy for AGC with DIC.

Murakami T, Murata T, Kawaguchi K, et al.
Cervical Cancer Patient-Derived Orthotopic Xenograft (PDOX) Is Sensitive to Cisplatinum and Resistant to Nab-paclitaxel.
Anticancer Res. 2017; 37(1):61-65 [PubMed] Related Publications
BACKGROUND: Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective.
MATERIALS AND METHODS: Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX.
RESULTS: H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors.
CONCLUSION: The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.

Li H, Lu Y, Pang Y, et al.
Propofol enhances the cisplatin-induced apoptosis on cervical cancer cells via EGFR/JAK2/STAT3 pathway.
Biomed Pharmacother. 2017; 86:324-333 [PubMed] Related Publications
OBJECTIVE: The main purpose of this study was to evaluate propofol and its combined effect with cisplatin on apoptosis of cervical cancer cells and molecular mechanisms of this phenomenon.
METHODS: The effects of propofol and cisplatin on cell viability and apoptosis were detected by cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry assay. Besides, protein expression of EGFR/JAK2/STAT3 pathway was determined by western blot. STAT3 was over-expressed in cervical cancer cells by STAT3 cDNA. Expression of EGFR and STAT3 protein of human tissues was evaluated by immunohistochemistry (IHC) assay.
RESULTS: In this study, we found that not only propofol alone could inhibit cervical cancer cells viability but also could increase the inhibitory effect of cisplatin on cervical cancer cells growth. Meanwhile, propofol sensitized cervical cancer cells to cisplatin-induced apoptosis but not affected normal cervical cells. In genetic level, propofol could enhance the anti-tumor effect of cisplatin through EGFR/JAK2/STAT3 pathway. Further studies indicated that overexpression of EGFR and STAT3 is related to poor prognoses in cervical cancer patients, which contributed to confirm the clinical role of combined application of propofol and cisplatin.
CONCLUSION: Propofol enhances the cisplatin-induced cell apoptosis cervical cancer cells via EGFR/JAK2/STAT3 pathway and may be developed as a potential therapeutic agent to treat cervical cancer.

Czarnomysy R, Surażyński A, Popławska B, et al.
Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells.
Mol Cell Biochem. 2017; 427(1-2):13-22 [PubMed] Free Access to Full Article Related Publications
The aim of our study was to determine whether the use of cisplatin in the presence echistatin in MDA-MB-231 breast cancer cells leads to a reduction of toxic effects associated with the use of cisplatin. The expression of β1-integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: protein kinase B (AKT), mitogen-activated protein kinases (ERK1/ERK2), nuclear factor kappa B (NFκB), and caspase-3 and -9 activity was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The viability of MDA-MB-231 breast cancer cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Annexin V-FITC/propidium iodide staining assay was performed to detect the induction of apoptosis. Inhibition DNA biosynthesis was determined by [(3)H]thymidine incorporation into DNA. The expression of of β1-integrin, IGF-IR, AKT, ERK1/ERK2, NFκB, caspase-3 and -9 was evaluated using Western blot. The results suggest that treatment of MDA-MB-231 breast cancer cells for 24 h cisplatin plus echistatin severely inhibits cell growth and activates apoptosis by upregulation of caspase-3 and -9 expressions. The effect was stronger than treatment cisplatin and echistatin alone. In this study, we have found that cisplatin plus echistatin treatment decreases collagen biosynthesis in MDA-MB-231 breast cancer cells stronger than the individual compounds. The inhibition was found to be dependent on the β1-integrin and IGF receptor activation. A significant reduction of ERK1/ERK2, AKT expression in cancer cells after cisplatin plus echistatin treatment was also found. The cancer cells treated by echistatin, cisplatin, and in particular the combination of both compounds drastically increased expression of NFκB transcription factor. Our results suggest that combined therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin. This mechanism probably is due to downregulation of expression of β1-integrin and IGF-IR receptors, and the signaling pathway proteins induced by these receptors. Our results suggest that therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin.

He CS, Liu YC, Xu ZP, et al.
Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3.
Cell Physiol Biochem. 2016; 40(5):1221-1229 [PubMed] Related Publications
BACKGROUND: Chemoresistance is a major obstacle to successful chemotherapy for human non-small cell lung cancer (NSCLC). Astragaloside IV, the component of Astragalus membranaceus, has been reported to exhibit anti-inflammation, anti-cancer and immunoregulatory properties. In the present study, we investigated the role of astragaloside IV in the chemoresistance to cisplatin in NSCLC cells.
METHODS: We established astragaloside IV-suppressed NSCLC cell lines including A549, HCC827, and NCI-H1299 and evaluated their sensitivity to cisplatin in vitro. In addition, we examined the mRNA and protein levels of B7-H3 in response to cisplatin-based chemotherapy.
RESULTS: We showed that high doses of astragaloside IV (10, 20, 40 ng/ml) inhibited NSCLC cell growth, whereas low concentrations of astragaloside IV (1, 2.5, 5 ng/ml) had no obvious cytotoxicity on cell viability. Moreover, combined treatment with astragaloside IV significantly increased chemosensitivity to cisplatin in NSCLC cells. On the molecular level, astragaloside IV co-treatment significantly inhibited the mRNA and protein levels of B7-H3 in the presence of cisplatin. In addition, ectopic expression of B7-H3 diminished the sensitization role of astragaloside IV in cellular responses to cisplatin in NSCLC cells.
CONCLUSION: These results demonstrate that astragaloside IV enhances chemosensitivity to cisplatin via inhibition of B7-H3 and that treatment with astragaloside IV and inhibition of B7-H3 serve as potential therapeutic approach for lung cancer patients.

Yu Y, Xie Q, Liu W, et al.
Increased intracellular Ca(2+) decreases cisplatin resistance by regulating iNOS expression in human ovarian cancer cells.
Biomed Pharmacother. 2017; 86:8-15 [PubMed] Related Publications
Previous studies have reported that intracellular Ca(2+) signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca(2+) and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDP(S)) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells. 2-Aminoethoxydiphenyl borate (2-APB) decreased cisplatin-induced iNOS expression and apoptosis in SKOV3 cells. Thus, iNOS induction may be a valuable strategy for improving the anti-tumor efficacy of cisplatin in ovarian cancer.

Dong Y, Wang M
Knockdown of TKTL1 additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells by regulating the levels of NADPH and ribose-5-phosphate.
Biomed Pharmacother. 2017; 85:672-678 [PubMed] Related Publications
BACKGROUND: Transketolase-like 1 (TKTL1) plays an important role in pentose phosphate pathway (PPP) branch, the main pathway generating nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotides for DNA synthesis. TKTL1 is closely related to DNA damage and has a close relationship with incidence and progression of cancers. Cisplatin is the main chemotherapeutic drug by inducing DNA damage. Whether TKTL1 knockdown additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells, however, remains largely undefined.
METHODS: Lipofectamine 2000 was used to transfect si-TKTL1s with different sequences into the CNE2 and HONE1 cells. The mRNA and protein levels of TKTL1 were determined by qRT-PCR and western blot, respectively. MTT assay and flow cytometry were used to access the viability and apoptosis of CNE2 and HONE1 cells. The NADPH and ribose-5-phosphate levels in both CNE2 and HONE1 cells were determined by NADPH examination kit and HPCE analysis, respectively. The effect of TKTL1 knockdown and NADPH/ribose-5-phosphate supplement on DNA damage was assessed by using Comet assay.
RESULTS: TKTL1 knockdown significantly decreased TKTL1 level in CNE2 and HONE1 cells. A significant decrease in cell viability and an obvious increase in cell apoptosis rate were found in si-TKTL1+cisplatin group compared with si-TKTL1 group or si-control+cisplatin group. The levels of NADPH and ribose-5-phosphate in CNE1 and HONE1 cells were dramatically decreased in si-TKTL1 group compared with si-control group. TKTL1 knockdown additively complemented cisplatin-induced cytotoxicity, which was partly reversed by the supplements of NADPH and ribose-5-phosphate, including the increased survival rate, decreased apoptosis and DNA damage.
CONCLUSIONS: Knockdown of TKTL1 additively complements cisplatin-induced cytotoxicity in the nasopharyngeal carcinoma cells by inhibiting the levels of NADPH and ribose-5-phosphate, indicating that TKTL1 may be a promising target to improve the therapeutic effect combining with cisplatin for the patients with nasopharyngeal carcinoma.

Miyoshi T, Misumi N, Hiraike M, et al.
Risk Factors Associated with Cisplatin-Induced Nephrotoxicity in Patients with Advanced Lung Cancer.
Biol Pharm Bull. 2016; 39(12):2009-2014 [PubMed] Related Publications
Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m(2) per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p<0.05). The cut-off value of Alb was 3.8 g/dL, calculated by receiver operating characteristics (ROC) curves. Multivariable logistic regression analysis revealed that cardiac disease (odds ratio=11.7; p=0.002) and hypoalbuminemia (odds ratio=6.99 p=0.025 significantly correlated with nephrotoxicity. In conclusion, cardiac disease and low baseline Alb values are possible risk factors for CIN.

Wu S, Zhang T, Du J
Ursolic acid sensitizes cisplatin-resistant HepG2/DDP cells to cisplatin via inhibiting Nrf2/ARE pathway.
Drug Des Devel Ther. 2016; 10:3471-3481 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Combinations of adjuvant sensitizers with anticancer drugs is a promising new strategy to reverse chemoresistance. Ursolic acid (UA) is one of the natural pentacyclic triterpene compounds known to have many pharmacological characteristics such as anti-inflammatory and anticancer properties. This study investigates whether UA can sensitize hepatocellular carcinoma cells to cisplatin.
MATERIALS AND METHODS: Cells were transfected with nuclear factor erythroid-2-related factor 2 (Nrf2) small interfering RNA and Nrf2 complementary DNA by using Lipofectin 2000. The cytotoxicity of cells was investigated by Cell Counting Kit 8 assay. Cell apoptosis, cell cycle, reactive oxygen species, and mitochondrial membrane potential were detected by flow cytometry fluorescence-activated cell sorting. The protein level of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and heme oxygenase-1 (HO-1) was detected by Western blot analysis.
RESULTS: The results showed that the reverse index was 2.9- and 9.69-fold by UA of 1.125 μg/mL and 2.25 μg/mL, respectively, for cisplatin to HepG2/DDP cells. UA-cisplatin combination induced cell apoptosis and reactive oxygen species, blocked the cell cycle in G0/G1 phase, and reduced the mitochondrial membrane potential. Mechanistically, UA-cisplatin dramatically decreased the expression of Nrf2 and its downstream genes. The sensibilization of UA-cisplatin combination was diminished in Nrf2 small interfering RNA-transfected HepG2/DDP cells, as well as in Nrf2 complementary DNA-transfected HepG2/DDP cells.
CONCLUSION: The results confirmed the sensibilization of UA on HepG2/DDP cells to cisplatin, which was possibly mediated via the Nrf2/antioxidant response element pathway.

Leekha A, Gurjar BS, Tyagi A, et al.
Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells through altered redox cycling and p53 upregulation.
J Cancer Res Clin Oncol. 2016; 142(12):2503-2514 [PubMed] Related Publications
PURPOSE: Cervical cancer is the second most prevalent cancer in women worldwide. Survival of patients has been improved by cisplatin-based chemotherapy, but its effectiveness is limited due to its adverse effects on many tissues, especially nephrotoxicity. To optimize the efficacy of CDDP, we propose a combination therapy using natural products with minimal side effects. Vitamin C being a natural antioxidant is capable of selectively targeting cancer cells at pharmacological concentrations. Vitamin C synergistically enhances the activity of chemotherapeutic agents without increasing toxicity to normal cells. Therefore, we exploited co-therapy with cisplatin and vitamin C to kill cervical cancer cells.
METHODS: We elucidated the role of CDDP and VC on cervical cancer cell line (SiHa) by using cell growth assays, DNA fragmentation analysis, comet assay, in vitro morphological assessment of apoptosis (AO/EB and DAPI staining), ROS analysis by DCFDA, flow cytometry, biochemical assays (GST, GSH, NO, catalase, TPA) and Western blotting.
RESULTS: Our results clearly demonstrated that CDDP and VC treatment exhibited ameliorative effect on induction of cell death by p53 overexpression and generation of hydrogen peroxide in SiHa cells, thereby reducing the dosage of CDDP required to induce cell death in cancer cells.
CONCLUSIONS: These studies provide novel approaches to combat cisplatin resistance in cervical cancer.

Cheng D, Xu Y, Sun C, He Z
MicroRNA-451 sensitizes lung cancer cells to cisplatin through regulation of Mcl-1.
Mol Cell Biochem. 2016; 423(1-2):85-91 [PubMed] Related Publications
As one of the most widely used chemotherapy drugs for lung cancer, chemoresistance of cisplatin (DPP) is one of the major hindrances in treatment of this malignancy. The microRNAs (miRNAs) have been identified to mediate chemotherapy drug resistance. MiR-451 as a tumor suppressor has been evaluated its potential effect on the sensitivity of cancer cells to DDP. However, the role of miR-451 in regulatory mechanism of chemosensitivity in lung cancer cells is still largely unknown. In this study, we first constructed a cisplatin-resistant A549 cell line (A549/DPP) accompanied with a decreased expression of miR-451 and an increased expression of Mcl-1in the drug resistant cells compared with the parental cells. Exogenous expression of miR-451 level in A549/DPP was found to sensitize their reaction to the treatment of cisplatin, which coincides with reduced expression of Mcl-1. Interestingly, Mcl-1 knockdown in A549/DPP cells increased the chemosensitivity to DPP, suggesting the dependence of Mcl-1 regulation in miR-451 activity. Moreover, miR-451 can restore cisplatin treatment response in cisplatin-resistant xenografts in vivo, while Mcl-1 protein levels were decreased. Thus, these findings provided that in lung cancer cells, tumor suppressor miR-451 enhanced DPP sensitivity via regulation of Mcl-1 expression, which could be served as a novel therapeutic target for the treatment of chemotherapy resistant in lung cancer.

Hayashi N, Kataoka H, Yano S, et al.
Anticancer Effects of a New Aminosugar-conjugated Platinum Complex Agent Against Cisplatin-resistant Gastric Cancer.
Anticancer Res. 2016; 36(11):6005-6009 [PubMed] Related Publications
BACKGROUND/AIM: Resistance against cisplatin is a problem for the success of gastric cancer chemotherapy. Herein, we evaluated the antitumor effect of a new aminosugar-conjugated, mono-functional platinum complex (Pt-Oqn), which forms a single covalent bond with DNA.
MATERIALS AND METHODS: We compared the cytotoxicity of Pt-Oqn to that of cisplatin (CDDP), oxaliplatin (L-OHP) and carboplatin (CBDCA). We also compared Pt-Oqn and cisplatin for DNA double-strand breaks based on phosphorylated histone H2AX levels in cancer cells and antitumor effects in xenograft models.
RESULTS: The resistance factor (RF) for Pt-Oqn was low among the four drugs, indicating the potential of Pt-Oqn for overcoming CDDP-induced resistance. In MKN45-R cells, γ-H2AX protein increased following treatment with Pt-Oqn, but not with cisplatin. Finally, Pt-Oqn, but not cisplatin, showed significant antitumor effects in MKN45-R xenografts.
CONCLUSION: This new aminosugar-conjugated platinum complex is a promising candidate agent for overcoming the drug resistance of cisplatin-resistant stomach cancer.

Jalota A, Kumar M, Das BC, et al.
Synergistic increase in efficacy of a combination of 2-deoxy-D-glucose and cisplatin in normoxia and hypoxia: switch from autophagy to apoptosis.
Tumour Biol. 2016; 37(9):12347-12358 [PubMed] Related Publications
Resistance to drugs, which is aggravated by hypoxia, is a well-known feature of tumors. The combination of drug exposure and hypoxia can give rise to several survival strategies in the exposed cells. Glioblastoma multiforme (GBM) is among the most hypoxic of solid tumors, and we have used glial cells to identify a drug combination that would be synergistically effective in these cells under both normoxia and hypoxia. Cisplatin (CP) and 2-deoxy-D-glucose (2-DG), which have been used for second-line therapy and for preclinical research, are relatively ineffective as single agents. During in vitro experiments with A172 and LN229 cells, there was increased resistance to both drugs under hypoxia. However, the combination of CP and 2-DG showed a synergistic effect in reducing cell viability under both normoxia and hypoxia, with a combination index of less than 1. Increased autophagy is a distinct feature of the response to 2-DG. However, autophagic markers were reduced, and apoptotic markers were upregulated by the combination, indicating a switch over from autophagic to apoptotic pathways with reduction in endoplasmic reticulum (ER) stress. The combination also resulted in a decrease of pAKT levels. The effect of CP in the combination was replicated by the prototype AKT inhibitor LY294002, further supporting the role of AKT inhibition in the synergism. Combination of 2-DG with CP, or possibly an AKT inhibitor, can prove to be an effective rational combination for reducing chemoresistance under both normoxic and hypoxic conditions in gliomas.

Zhang L, Liu X, Tang Z, et al.
Reversal of galectin-1 gene silencing on resistance to cisplatin in human lung adenocarcinoma A549 cells.
Biomed Pharmacother. 2016; 83:265-270 [PubMed] Related Publications
This study aims to investigate reversal of Galectin-1 gene silencing on resistance to cisplatin in human lung adenocarcinoma A549 (or A549/DDP) in vivo and in vitro. The stably transfected lentivirus vector was used to silence Galectin-1 in human lung adenocarcinoma cell line A549 and A549/DDP cells and the cell lines were cultured and passaged. RT-PCR and western blot assay were used to test A549, A549/DDP cells, silenced Galectin-1A549 (A549/I) cells, Galectin-1 mRNA and protein expression levels, respectively, in A549/DDP (A549/DDP/I) cells. CCK8 assay was used to measure median inhibitory concentration (IC50) in each group and resistant index of A549/DDP cells and A549/DDP/I cells. Tumor model in nude mice was established by armpit injection of A549, A549/DDP, A549/I, A549/DDP/I cells. Cisplatin was injected intraperitoneally in tumor models and growth of tumor was observed in vivo model. Four weeks later, nude mice were killed and tumor weight and diameter was measured. mRNA and protein expression of Galectin-1 in A549/DDP cells was higher than that in A549 cells. mRNA and protein expression of Galectin-1 in A549/DDP/I cells was lower than that in A549/DDP cells. Moreover, IC50 values ​​and resistance index in A549/DDP cells was higher than that in A549 cells group and IC50 values ​​and resistance index A549/DDP/I cell group were lower than that in A549/DDP cells. Additionally, tumor weight and volume in A549/DDP/I cell group were lower than that in A549/DDP. In conclusion, Galectin-1 gene silencing would improve the sensitivity of A549/DDP cells to cisplatin in vivo and in vitro.

Park K, Kim KP, Park S, Chang HM
Comparison of gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer.
Asia Pac J Clin Oncol. 2017; 13(1):13-20 [PubMed] Related Publications
AIM: It remains unclear whether capecitabine combined with cisplatin would show similar effects compared with standard therapy using gemcitabine and cisplatin in advanced biliary tract cancer (BTC).
METHODS: Patients with advanced BTC who were treated with first-line chemotherapy at Asan Medical Center were retrospectively analyzed. All patients received either cisplatin followed by gemcitabine on days 1 and 8 every 3 weeks (GP group), or capecitabine on days 1-14 with cisplatin on day 1 every 3 weeks (XP group).
RESULTS: Of the 134 patients who met the inclusion criteria, 78 received XP and 56 were treated with GP. After a median follow-up of 26.2 months, the progression-free survival was 5.7 months for XP versus 4.1 months for GP (hazard ratio [HR] = 0.81, P = 0.31). The overall survival (OS) was 11.0 months for XP versus 9.8 months for GP (HR = 0.84, P = 0.36). In the multivariate analysis, there were no significant differences in PFS and OS between the two groups.
CONCLUSION: XP seems to be as effective as GP in patients with advanced BTC. The XP regimen is feasible and might offer increased convenience regarding the schedule of drug administration.

Caroline B, Sundus Y, Dawn D, et al.
Cost analysis of cetuximab (Erbitux) plus radiotherapy (ERT) versus concomitant cisplatin plus radiotherapy (CRT) within an NHS oncology unit (single institution): a pilot study.
Br J Radiol. 2016; 89(1068):20160105 [PubMed] Related Publications
OBJECTIVE: The aim of this feasibility study is to define the resource effectiveness of cetuximab vs cisplatin given concomitantly with radiotherapy for squamous cell carcinoma within a National Health Service clinical oncology unit.
METHODS: 20 patients with Stage 3 or 4 head and neck squamous cell cancers were randomized to receive either cetuximab with radiotherapy (ERT) or cisplatin with radiotherapy concurrent with external beam radiotherapy 70 Gy in 35 fractions on a 1 : 1 basis over a 12-month duration. The study compared the resource utilization of ERT vs cisplatin with radiotherapy taking into account drug costs, clinical management and the costs of managing treatment-related toxicity from first fraction of radiotherapy to 6 months after the completion of therapy. Outcome measures were quality of life (recorded at the entry, end of radiotherapy, 6 weeks post treatment and 6 months post treatment), admissions to hospital, delays to radiotherapy, locoregional control and survival.
RESULTS: Total drug costs including cost of nutritional supplements for patients treated with cetuximab were £7407.45 compared with £3959.07 for patients treated with cisplatin. Unscheduled admissions for toxicity management were significantly more common in the ERT arm. Healthcare personnel spent significantly more time delivering unscheduled outpatient care for patients receiving cisplatin than for those receiving cetuximab (p = 0.01). No significant difference in the quality of life was suggested at baseline, 6 weeks and 6 months. The mean time to removal of percutaneous gastrostomy (PEG) after completion of radiotherapy was 49.7 weeks in the cisplatin arm and 18.5 weeks in the cetuximab arm (p = 0.04). There was a statistically significant difference in patient-reported use of PEG between the cisplatin and cetuximab arms at 6 months following completion of treatment (p = 0.04). At 21 months, overall survival was 80% in the cisplatin arm vs 50% in the cetuximab (p = 0.332), with disease-free survival being 80% in the cisplatin arm vs 40% in the cetuximab (p = 0.097).
CONCLUSION: Cetuximab is still more expensive in simple drug cost terms than cisplatin when delivered with radiotherapy taking into account costs of drugs for toxicity management and nutritional supplements but other resource implications such as inpatient admission, time spent delivering unscheduled care and cost of additional investigations to manage toxicity for patients treated with cisplatin significantly reduce differential. The study suggested significant differences in patient-reported PEG use at 6 months and in time to PEG removal in favour of the cetuximab arm. Advances in knowledge: There is paucity of randomized data on cost analysis for cisplatin vs cetuximab radiotherapy; this trial informs on the cost analysis between the two approaches.

Sanie-Jahromi F, Saadat I, Saadat M
Effects of extremely low frequency electromagnetic field and cisplatin on mRNA levels of some DNA repair genes.
Life Sci. 2016; 166:41-45 [PubMed] Related Publications
AIMS: It has been shown that exposure to extremely-low frequency (˂300Hz) oscillating electromagnetic field (EMF) can affect gene expression. The effects of different exposure patterns of 50-Hz EMF and co-treatment of EMF plus cisplatin (CDDP) on mRNA levels of seven genes involved in DNA repair pathways (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) were evaluated.
MAIN METHODS: Two 50-Hz EMF intensities (0.25 and 0.50mT), three exposure patterns (5min field-on/5min field-off, 15min field-on/15min field-off, 30min field-on continuously) and two cell lines (MCF-7 and SH-SY5Y) were used. The mRNA levels were measured using quantitative real-time PCR.
KEY FINDINGS: The examined genes had tendency to be down-regulated in MCF-7 cells treated with EMF. In the pattern of 15min field-on/15min field-off of the 0.50mT EMF, no increase in mRNA levels were observed, but the mRNA levels of GADD45A, XRCC1, XRCC4, Ku80, Ku70, and LIG4 were down-regulated. A significant elevation in IC50 of CDDP was observed when MCF-7 and SH-SY5Y cells were co-treated with CDDP+EMF in comparison with the cells treated with CDDP alone. GADD45A mRNA levels in MCF-7 and SH-SY5Y cells co-treated with CDDP+EMF were increased and at the same time the mRNA levels of XRCC4, Ku80, Ku70 and DNA-PKcs were down-regulated.
SIGNIFICANCE: Present study provides evidence that co-treatment of CDDP+EMF can enhance down-regulation of the genes involved in non-homologous end-joining pathway. It might be suggested that co-treatment of CDDP+EMF could be more promising for sensitizing cancer cells to DNA double strand breaks.

Yu N, Dou L, Li Y, et al.
Roles of ERα and ERβ in estrogen-induced DDP chemoresistance in non-small cell lung cancer.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
The role of estrogen in inducing chemoresistance is not yet fully understood. The objective of this study was to observe the relationship between estrogen levels and cellular response to chemotherapeutic drugs in non-small cell lung cancer (NSCLC) and to reveal the potential mechanisms involved. Cell viability was analyzed after pre-treating NSCLC cells with different levels of estrogen (E2), followed by treatment with an anti-tumor drug for 48 h. The roles of various estrogen receptors (ERs) were examined in vitro by blocking the activity of each ER individually. The ER pathway was further confirmed in NSCLC tissues. It was found that 10-1000 nM E2 resulted in a decreased cellular response to DDP in H1650 cells compared to the use of cisplatin alone (P < 0.05). However, this result was not demonstrated in H1299 cells, which lack p53. Both ERa and ERb were associated with E2-induced cisplatin chemoresistance, though they had opposite functions. p53 expression did not correlate with the expression of ERa or ERb individually. However, a statistically significant correlation between p53 expression and ERa to ERb mRNA ratio was observed (P < 0.001, R = -0.676). These findings suggest that E2-induced DDP chemoresistance depends on the balance between ERa and ERb expression and the p53 pathway.

Rades D, Seidl D, Janssen S, et al.
Comparing two lower-dose cisplatin programs for radio-chemotherapy of locally advanced head-and-neck cancers.
Eur Arch Otorhinolaryngol. 2017; 274(2):1021-1027 [PubMed] Related Publications
Radio-chemotherapy is a common treatment for locally advanced squamous cell head-and-neck cancers (LA-SCCHN). Cisplatin (100 mg/m(2)) every 3 weeks is very common but associated with considerable toxicity. Therefore, cisplatin programs with lower daily doses were introduced. There is a lack of studies comparing lower-dose programs. In this study, 85 patients receiving radio-chemotherapy with 20 mg/m(2) cisplatin on 5 days every 4 weeks (group A) were retrospectively compared to 85 patients receiving radio-chemotherapy with 30-40 mg/m(2) cisplatin weekly (group B). Groups were matched for nine factors including age, gender, performance score, tumor site, T-/N-category, surgery, hemoglobin before radio-chemotherapy, and radiation technique. One- and 3-year loco-regional control rates were 83 and 69 % in group A versus 74 and 63 % in group B (p = 0.12). One- and 3-year survival rates were 93 % and 73 % in group A versus 91 and 49 % in group B (p = 0.011). On multivariate analysis, survival was significantly better for group A (HR 1.17; p = 0.002). In groups A and B, 12 and 28 % of patients, respectively, did not receive a cumulative cisplatin dose ≥180 mg/m(2) (p = 0.016). Toxicity rates were not significantly different. On subgroup analyses, group A patients had better loco-regional control (p = 0.040) and survival (p = 0.005) than group B patients after definitive radio-chemotherapy. In patients receiving adjuvant radio-chemotherapy, outcomes were not significantly different. Thus, 20 mg/m(2) cisplatin on 5 days every 4 weeks resulted in better loco-regional control and survival in patients receiving definitive radio-chemotherapy and may be preferable for these patients. Confirmation of these results in a randomized trial is warranted.

Sautois B, Schroeder H, Martin M, et al.
Weekly cisplatin with radiotherapy for locally advanced head and neck squamous cell carcinoma.
J BUON. 2016 Jul-Aug; 21(4):979-988 [PubMed] Related Publications
PURPOSE: Although commonly used for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) concomitant radio-chemotherapy (RT-CT) with weekly cisplatin has not been definitely studied. We conducted a single centre retrospective study with the aim to evaluate efficacy and acute toxicity of definitive concomitant RT-CT with 40 mg/m(2) weekly cisplatin in patients with locally advanced HNSCC with a particular emphasis on RT modality (conventional or accelerated) and dose of cisplatin delivered.
METHODS: One hundred and twelve consecutive patients were included. They were given cisplatin 40 mg/m(2))week concomitantly with conventionally fractionated (CFRT) (N=33) or accelerated (ART) (N=79) RT.
RESULTS: RT was delivered according to the treatment plan in 104 patients and full dose was given to 107 patients. A median cumulative cisplatin dose of 240 mg/m(2) was administered to patients treated with CFRT and of 200 mg/m(2) to those treated with ART. Overall complete response rate was 81.3%. With a median follow up of 38.4 months, median overall survival (OS) was 75 months, not influenced by RT type or cisplatin dose received. The most clinically significant grade 3 or 4 acute toxicities were stomatitis (35.7%), neutropenia (25%), anemia (12.5%) and acute kidney injury (5.4%).
CONCLUSIONS: Our study shows that a median cumulative dose of 200 mg/m(2) cisplatin can be safely administered using a weekly regimen to patients treated with concomitant RT (CFRT or ART). Efficacy results and toxicity compare favorably with those described with triweekly cisplatin RT-CT, suggesting that a randomized comparison should be undertaken.

Wu X, Huang J, Liu L, et al.
Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma: A retrospective matched case-control study.
Medicine (Baltimore). 2016; 95(39):e4926 [PubMed] Free Access to Full Article Related Publications
To evaluate the treatment efficacies and toxicities of concurrent cetuximab-based bioradiotherapy (BRT) or cisplatin-based chemoradiotherapy (CRT) in locally advanced nasopharyngeal carcinoma. :Patients with previously untreated locally advanced nasopharyngeal carcinoma were matched into pairs, and enrolled into the study. All patients were given either BRT or CRT. Survival outcomes, toxicities, and prognostic factors were evaluated. :A total of 112 patients were enrolled. The 5-year overall survival was 79.3% and 79.5% in CRT and BRT arm, respectively (P = 0.797) and the 5-year DFS was 73.5% and 74.6%, respectively (P = 0.953). In toxicity analysis, CRT arm had more significant decrease in white blood cell, platelet, hemoglobin, and severe vomiting, while more severe skin reactions and mucositis were shown in BRT arm. :BRT was not less efficacious than traditional CRT. They lead to different aspects of toxicities. If patients cannot stand more severe toxicities caused by CRT, BRT could be an ideal alternative.

Wang Z, Liu S, Ding K, et al.
Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells.
Tumour Biol. 2016; 37(11):15133-15143 [PubMed] Related Publications
Renal cell carcinoma (RCC) accounts for 3 % of all adult malignancies and is the most lethal urological cancer. Livin is a member of the inhibitor of apoptosis protein (IAP) family, which is associated with tumor resistance to radiotherapy and chemotherapy. Clinical data also showed that patients with high tumor grades and stages have higher expression levels of Livin in RCC cells. Autophagy is a survival mechanism activated in response to nutrient deprivation. A possible role of Livin in the autophagy of RCC cells has not been investigated; therefore, this pioneer study was carried out. Livin was silenced in RCC cells (slow virus infection [SVI]-shLivin cells) by lentiviral transfection. Then, mRNA and protein expression levels in the transfected cells were assessed by quantitative fluorescence PCR and Western blotting, respectively. In addition, acridine orange staining and electron microscopy were used to assess autophagy in SVI-shLivin cells. The cisplatin IC50 values for RCC cells were measured by the CCK8 assay. Potent antitumor activities were observed in xenograft mouse models generated with Livin-silenced RCC cells in terms of delayed tumor onset and suppressed tumor growth. These results suggested that Livin silencing could increase the chemotherapeutic sensitivity of RCC cells to cisplatin and induce autophagic cell death. A possible mechanism of Bcl-2 and Akt pathway involvement was discussed specifically in this study. Overall, Livin silencing induces apoptotic and autophagic cell death and increases chemotherapeutic sensitivity of RCC cells to cisplatin.

Mahlberg R, Lorenzen S, Thuss-Patience P, et al.
New Perspectives in the Treatment of Advanced Gastric Cancer: S-1 as a Novel Oral 5-FU Therapy in Combination with Cisplatin.
Chemotherapy. 2017; 62(1):62-70 [PubMed] Related Publications
Oral fluoropyrimidines have been available for more than 10 years. Capecitabine is well established in treating solid tumors in Europe. S-1 (Teysuno®), an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, has not been available in non-Asia countries until recently. In Japan, S-1 in combination with cisplatin is the recommended first-line treatment in patients with gastric cancer. In Europe, the first trials with S-1 were disappointing due to high unacceptable incidences of adverse events. Pharmacokinetic studies showed differences in Asian and Caucasian patients; therefore, a new non-Asian study program was initiated, which led to the pivotal phase 3 trial First-Line Advanced Gastric Cancer Study (FLAGS). In FLAGS, 1,053 patients with advanced gastric cancer from 24 non-Asian countries were enrolled. S-1 plus cisplatin showed no overall survival (OS) benefit when compared to 5-FU plus cisplatin. The primary endpoint superior OS was not met but better tolerability was shown. A post hoc noninferiority OS and safety analysis showed that S-1 plus cisplatin has the same efficacy as 5-FU plus cisplatin but a more favorable safety profile. This led to the approval of S-1 in combination with cisplatin in gastric cancer in Europe in 2011. This article reviews the mode of action of S-1, pivotal study results from an EU point of view, and future perspectives.

Sun Y, Jin L, Liu JH, et al.
Interfering EZH2 Expression Reverses the Cisplatin Resistance in Human Ovarian Cancer by Inhibiting Autophagy.
Cancer Biother Radiopharm. 2016; 31(7):246-52 [PubMed] Related Publications
We aimed to determine the effects of the inhibition of enhancer of zeste homolog 2 (EZH2) gene expression on the cisplatin resistance of the human ovarian cancer cell line, SKOV3/DDP, and to identify the underlying mechanisms. SKOV3/DDP cells were stably transfected with pSUPER-EZH2 (EZH2 RNA interference plasmid) or pcDNA3.1-EZH2 (EZH2 gene overexpression plasmid) using the lipofection method. Real-time fluorescence quantitative reverse transcription polymerase chain reaction and western blotting confirmed that EZH2 expression was downregulated in pSUPER-EZH2-transfected cells. Flow cytometry revealed that EZH2 inhibition did not induce apoptosis, but significantly inhibited autophagy. In addition, it significantly increased the expression of the cellular senescence-signaling proteins p14(ARF), p16(INK4a), p53, pRb, and p21, and significantly decreased the expression of cyclin-dependent kinase (CDK)1, CDK2, and H3K27me3. Cellular senescence was characterized by a significant increase in the G0/G1 ratio and the restoration of sensitivity to cisplatin in the drug-resistant cells. These findings suggest that interfering with EZH2 expression can inhibit SKOV3/DDP cell autophagy and reverse resistance to cisplatin. The underlying mechanisms could be associated with the regulation of the cellular senescence-signaling pathway.

Feng J, Xu J, Wang X, Zhao D
S-1 plus cisplatin with concurrent radiotherapy versus cisplatin alone with concurrent radiotherapy in Chinese patients with nonsmall-cell lung cancer: A multicentre randomized controlled trial.
Medicine (Baltimore). 2016; 95(36):e4557 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The aim of this study was to investigate the efficacy and safety of S-1 plus cisplatin combined with concurrent radiotherapy (SCCCR) versus cisplatin alone combined with concurrent radiotherapy (CCCR) in Chinese patients with unresectable stage III nonsmall-cell lung cancer (NSCLC).
METHODS: Between January 2012 and December 2014, 72 eligible Chinese patients with NSCLC were included and randomly divided into 2 groups, each having 36 patients. Patients in the SCCCR group received S-1 plus cisplatin with concurrent, radiotherapy. The other 36 patients in the CCCR group were administered cisplatin with concurrent radiotherapy. The primary outcome was the overall response rate. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events.
RESULTS: The 3-year overall response rates for the SCCCR and CCCR groups were 60.1% and 53.3%, respectively (P = 0.041). The median OS was 35.1 (range, 6.5-47.2) months and 24.6 (range, 2.8-24.3) months for the SCCCR and CCCR groups, respectively (P = 0.016). The median PFS for the SCCCR and CCCR groups was 31.4 (range, 5.6-39.3) months and 22.3 (range, 2.4-36.5) months, respectively (P = 0.023). The toxicity profiles were similar for both groups.
CONCLUSION: The efficacy and safety of SCCCR was more encouraging compared to those of CCCR in Chinese NSCLC patients. In addition, the toxicities in both groups were tolerable.

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