Aich RK, Dasgupta S, Chakraborty B, et al.
Primary fallopian tube carcinoma with metastasis in the contralateral ovary.
J Indian Med Assoc. 2012; 110(7):494-5, 498 [PubMed]

Primary malignant neoplasm of the fallopian tube is one of the rarest gynaecological malignancies and a pre-operative diagnosis is often missed due to its diagnostic confusion with the tubo-ovarian mass, hydrosalpinx, ectopic pregnancy and ovarian malignancy. Transcoelomic, lymphatic, transluminal and haematogenous spread may occur to the other abdominal and pelvic organs as well as to the distant sites. Though the body of the uterus, ovaries and the contralateral fallopian tube are frequently involved, in the present case the contralateral ovary was the only site of involvement which is very unusual.

Nezhat FR, Denoble SM, Cho JE, et al.
Safety and efficacy of video laparoscopic surgical debulking of recurrent ovarian, fallopian tube, and primary peritoneal cancers.
JSLS. 2012 Oct-Dec; 16(4):511-8 [PubMed] Free Access to Full Article

BACKGROUND AND OBJECTIVE: Studies on the role of laparoscopy in secondary or tertiary cytoreduction for recurrent ovarian cancer are limited. Our objective is to describe our preliminary experience with laparoscopic secondary/tertiary cytoreduction in patients with recurrent ovarian, fallopian, and primary peritoneal cancers.
METHODS: This is a retrospective analysis of a prospective case series. Women with recurrent ovarian, fallopian tube, or primary peritoneal cancers deemed appropriate candidates for laparoscopic debulking by the primary surgeon(s) were recruited. The patients underwent exploratory video laparoscopy, biopsy, and laparoscopic secondary/tertiary cytoreduction between June 1999 and October 2009. Variables analyzed include stage, site of disease, extent of cytoreduction, operative time, blood loss, length of hospital stay, complications, and survival time.
RESULTS: Twenty-three patients were recruited. Only one surgery involved conversion to laparotomy. Seventeen (77.3%) of the patients had stage IIIC disease at the time of their initial diagnosis, and 20 (90.9%) had laparotomy for primary debulking. Median blood loss was 75 mL, median operative time 200 min, and median hospital stay 2 d. No intraoperative complications occurred. One patient (4.5%) had postoperative ileus. Eighteen (81.8%) of the patients with recurrent disease were optimally cytoreduced to 1cm. Overall, 12 patients have no evidence of disease (NED), 6 are alive with disease (AWD), and 4 have died of disease (DOD), over a median follow-up of 14 mo. Median disease-free survival was 71.9 mo.
CONCLUSIONS: In a well-selected population, laparoscopy is technically feasible and can be utilized to optimally cytoreduce patients with recurrent ovarian, fallopian, or primary peritoneal cancers.

Schilder RJ, Sill MW, Lankes HA, et al.
A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: a Gynecologic Oncology Group study.
Gynecol Oncol. 2013; 129(1):86-91 [PubMed]

OBJECTIVES: Vascular endothelial growth factors (VEGF) and their receptors have a critical role in stimulating the growth of ovarian cancer cells. Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1-3, as well as c-KIT and platelet-derived growth factor which are related to the VEGF family.
PATIENTS AND METHODS: Twenty-two eligible patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib. Peripheral blood was analyzed for circulating tumor cells (CTC) and circulating endothelial cells/circulating endothelial progenitors (CEC/CEP), VEGF levels and cell-free circulating DNA (cfDNA).
RESULTS: The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome. One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment. Twelve of the 22 patients (50%) had indeterminate responses at trial closure. Early closure without clinical efficacy data precludes meaningful correlative studies.
CONCLUSIONS: The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population. There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers.

Bamias A, Bamia C, Zagouri F, et al.
Improved survival trends in platinum-resistant patients with advanced ovarian, fallopian or peritoneal cancer treated with first-line paclitaxel/platinum chemotherapy: the impact of novel agents.
Oncology. 2013; 84(3):158-65 [PubMed]

OBJECTIVE: The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy.
METHODS: Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995-31/12/2001 (n = 56) and Group B 1/1/2002-24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time.
RESULTS: MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001).
CONCLUSIONS: The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients.

Kaur H, Levinsky E, Colgan TJ
Papillary syncytial metaplasia of fallopian tube endometriosis: a potential pitfall in the diagnosis of serous tubal intraepithelial carcinoma.
Arch Pathol Lab Med. 2013; 137(1):126-9 [PubMed]

Histopathologic diagnosis of tubal intraepithelial carcinoma (TIC) has emerged as a significant challenge in the last few years. The avoidance of pitfalls in the diagnosis of TIC is crucial if a better understanding of its natural history and outcome is to be achieved. Herein, we present a case of a 52-year-old woman who underwent a risk-reducing salpingo-oophorectomy procedure. Histologic examination of a fallopian tube demonstrated a focus of atypical epithelial proliferation, which was initially considered to be a TIC. Complete study of the case indicated that the focus was, in fact, papillary syncytial metaplasia of tubal mucosal endometriosis. Papillary syncytial metaplasia may resemble TIC and should be considered in cases of proliferative lesions of the tubal epithelium.

Lengyel E, Fleming S, McEwen KA, et al.
Serial sectioning of the fallopian tube allows for improved identification of primary fallopian tube carcinoma.
Gynecol Oncol. 2013; 129(1):120-3 [PubMed]

OBJECTIVE: Serial sectioning of the fallopian tube in women undergoing risk reducing surgery has been shown to increase the detection rate of occult malignancy in BRCA mutation carriers. We undertook this study to determine whether this protocol at the time of surgery for ovarian cancer (OV) or primary peritoneal malignancies (PP) changes the detection rate of fallopian tube carcinoma (FT). We secondarily investigated where this difference affects patient outcomes.
METHODS: A retrospective review of 130 patients treated at the University of Chicago Medical Center for ovarian, peritoneal or fallopian tube carcinoma was conducted. Sixty five patients diagnosed with OV, PP or FT who had serial sectioning of the fallopian tubes at the time of diagnoses (SS) were compared to 65 patients whose fallopian tubes were sectioned in a standard fashion (PSS).
RESULTS: Serial sectioning of the fallopian tube at the time of pathologic examination in women with presumed OV or PP led to an increase in the number of women diagnosed with FT as the primary site of origin (p<0.001). Clinical or pathologic risk factors leading to an increased risk of FT were not identified. Survival between the two groups was similar.
CONCLUSION: In women with presumed OV or PP, serial sectioning identifies women with FT. FT may be more common than previously noted; however distinct biologic or clinical behavior to differentiate it from OV or PP could not be identified. Clinical management of FT should continue to be the same as that of OV or PP.

Nezhat CH, Dun EC, Wieser F, Zapata M
A rare case of primary extranodal marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix in the setting of endometriosis.
Am J Obstet Gynecol. 2013; 208(1):e12-4 [PubMed]

Extranodal marginal zone B-cell lymphomas are uncommon. Most occur in the gastrointestinal tract. Marginal zone B-cell lymphomas of the female genital tract are rare, and few cases exist of marginal zone B-cell lymphomas of the uterus, cervix, and fallopian tubes. We report the first marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix arising in endometriosis.

Tanner EJ, Long KC, Feffer JB, et al.
Parenchymal splenic metastasis is an independent negative predictor of overall survival in advanced ovarian, fallopian tube, and primary peritoneal cancer.
Gynecol Oncol. 2013; 128(1):28-33 [PubMed]

OBJECTIVE: The purpose of this study was to evaluate the significance of parenchymal splenic metastasis (PSM) in ovarian (OC), fallopian tube (FTC), and primary peritoneal cancer (PPC).
METHODS: All patients with stage IIIB-IV OC, FTC, and PPC undergoing primary cytoreduction from 2001 to 2010 at our institution were identified. In patients undergoing splenectomy, pathology was reviewed for the presence of PSM. Multivariate Cox regression and Kaplan-Meier survival analysis were used to evaluate factors associated with overall survival (OS).
RESULTS: Of 576 patients identified, stage was: IIIB - 23 (4%), IIIC - 468 (81.2%), and IV - 85 (14.8%). Optimal cytoreduction was achieved in 430 patients (74.7%), including 85 of 97 patients (87.6%) undergoing splenectomy. PSM was identified in 20 patients (20.6%) undergoing splenectomy, including 3 of 5 patients (60%) with radiographically identified parenchymal liver metastases and 17 of 92 patients (18.5%) without such radiographic findings (P=0.059). Age, preoperative albumin, residual disease, stage, bulky upper abdominal disease, IP chemotherapy, and PSM were associated with OS on univariate analysis. Splenectomy was not associated with survival. Age, preoperative albumin, residual disease, stage, and PSM (HR=0.46; 95% CI, 0.27-0.77) were associated with OS on multivariate analysis. In the subset of patients undergoing splenectomy, OS was lower for patients with PSM versus those without PSM (28.5 v 51.2months, P=0.004).
CONCLUSIONS: PSM is independently associated with decreased OS in patients with advanced OC, FTC, and PPC. PSM occurs in the setting of other evidence of hematogenously disseminated disease, but also occurs outside this setting. PSM should be considered a criterion for stage IV disease.

Colombo N, Kutarska E, Dimopoulos M, et al.
Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer.
J Clin Oncol. 2012; 30(31):3841-7 [PubMed]

PURPOSE: This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer.
PATIENTS AND METHODS: Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).
RESULTS: A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm.
CONCLUSION: Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.

Luyckx M, Leblanc E, Filleron T, et al.
Maximal cytoreduction in patients with FIGO stage IIIC to stage IV ovarian, fallopian, and peritoneal cancer in day-to-day practice: a Retrospective French Multicentric Study.
Int J Gynecol Cancer. 2012; 22(8):1337-43 [PubMed]

OBJECTIVES: To evaluate the outcome of maximal cytoreductive surgery in patients with stage IIIC to stage IV ovarian, tubal, and peritoneal cancer regarding overall survival (OS) and disease-free survival (DFS).
MATERIALS AND METHODS: Five hundred twenty-seven patients with stage IIIC (peritoneal) and stage IV (pleural) ovarian, fallopian tube, and peritoneal carcinoma underwent surgery between January 2003 and December 2007 in 7 gynecologic oncology centers in France. Patients undergoing primary and interval debulking surgery were included, whichever the number of chemotherapy cycles. The extent of disease, type of surgical procedure, and amount of residual disease were recorded. A multivariate analysis of the outcome was performed, taking into account the stage, grade, and timing of surgery.
RESULTS: Median DFS was 17.9 months, but median OS was not reached at the time of analysis. Complete cytoreductive surgery, without evident residual tumor at the end of the procedure, was obtained in 71% of all patients (primary surgery, 33%). After neoadjuvant therapy, the rate of complete debulking surgery was higher (74%) compared to primary cytoreductive surgery (65%). Twenty-three percent of patients needed "ultra radical surgery" to achieve this goal. The most significant predictive factor for DFS and OS was complete cytoreductive surgery compared to any amount, even minimal (1-10 mm), of residual disease. In the group of patients with complete cytoreductive surgery, the patients undergoing surgery before chemotherapy showed better DFS than those having first chemotherapy.
CONCLUSION: The findings confirm that complete cytoreduction is the criterion standard of surgery in the management of advanced ovarian, peritoneal, and fallopian tube cancer, whatever the timing of surgery. With experienced teams, surgery was completed, without evident residual tumor in 71% of the cases.

Gould N, Sill MW, Mannel RS, et al.
A phase I study with an expanded cohort to assess feasibility of intravenous docetaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with previously untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
Gynecol Oncol. 2012; 127(3):506-10 [PubMed]

OBJECTIVE: To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) docetaxel, intraperitoneal (IP) carboplatin and IP paclitaxel in women with stage II-IV untreated ovarian, fallopian tube or primary peritoneal carcinoma.
METHODS: Patients received docetaxel (55-75 mg/m(2)) IV and carboplatin (AUC 5-7) IP on day 1 and paclitaxel 60 mg/m(2) IP on day 8. A standard 3+3 design was used in the dose escalation phase. A 2-stage group sequential design with 20 patients at the MTD was used in the feasibility phase.
RESULTS: The MTD determined during the dose escalation phase was day 1 docetaxel 75 mg/m(2) IV, carboplatin AUC 6 IP and day 8 IP paclitaxel 60 mg/m(2). Forty-six patients were enrolled in the feasibility portion at this dose level. Six were unevaluable. Fifteen evaluable patients had dose-limiting toxicities (DLTs) within the first four cycles. These DLTs were prolonged neutropenia (2), neutropenic fever (7), grade 4 thrombocytopenia (1), grade 4 dehydration (1), grade 3 infection (2), grade 3 oral mucositis (1) and pulmonary embolism (1).
CONCLUSIONS: Docetaxel 75 mg/m(2) IV, carboplatin AUC 6 IP administered on day 1, and paclitaxel 60 mg/m(2) IP administered on day 8, is the MTD when considering one cycle of treatment but was not feasible over four cycles due to bone marrow toxicity. We recommend reduction of carboplatin to AUC 5 should this regimen be considered for treatment in women with newly diagnosed advanced ovarian cancer.

Reitsma W, de Bock GH, Oosterwijk JC, et al.
Support of the 'fallopian tube hypothesis' in a prospective series of risk-reducing salpingo-oophorectomy specimens.
Eur J Cancer. 2013; 49(1):132-41 [PubMed]

OBJECTIVE: To determine the prevalence, localisation and type of occult (non)invasive cancer in risk-reducing salpingo-oophorectomy (RRSO) specimens in BRCA-mutation carriers and high-risk women from BRCA-negative families.
METHODS: A consecutive series of RRSO specimens of asymptomatic, screen-negative high-risk women were prospectively collected in our tertiary multidisciplinary cancer clinic from January 2000 until March 2012. All high-risk women in this study underwent genetic testing on BRCA-mutations. The surgico-pathological protocol comprised complete resection of ovaries and fallopian tubes, transverse sectioning at 2-3 mm (sectioning and extensively examining the fimbrial end [SEE-FIM] protocol from 2006) and double independent pathology review of morphologically deviant sections.
RESULTS: Three hundred and sixty RRSOs were performed in 188 BRCA1-carriers, 115 BRCA2-carriers and 57 BRCA-negative women at a median age of 44.0 years. Four occult invasive cancers were detected in BRCA-carriers (1.3%, 95%-confidence interval (CI) 0.03-2.61), all in BRCA1-carriers >40 years of age. All cancers, of which two tubal and two ovarian cancers, were FIGO-stage I/II. Three non-invasive serous intraepithelial carcinomas (STICs) were detected in BRCA-carriers (1.0%, 95%-CI 0.00-2.10). In BRCA-negative women one STIC was found (1.8%, 95%-CI 0.00-5.16), however she carried an unclassified variant in BRCA2. Total follow-up after RRSO was 1691 woman-years, in which one BRCA1-carrier developed peritoneal cancer (0.3%, 95%-CI 0.00-0.82).
CONCLUSIONS: A low prevalence of occult invasive cancer (1.1%) was found in young asymptomatic, screen-negative women at increased ovarian cancer risk undergoing RRSO. This study adds to the advice to perform RRSO in BRCA1-carriers before the age of 40. Our findings support the hypothesis of the fallopian tube as the primary site of origin of pelvic high-grade serous cancer.

Paik DY, Janzen DM, Schafenacker AM, et al.
Stem-like epithelial cells are concentrated in the distal end of the fallopian tube: a site for injury and serous cancer initiation.
Stem Cells. 2012; 30(11):2487-97 [PubMed]

The reproductive role of the fallopian tube is to transport the sperm and egg. The tube is positioned to act as a bridge between the ovary where the egg is released and the uterus where implantation occurs. Throughout reproductive years, the fallopian tube epithelium undergoes repetitive damage and regeneration. Although a reservoir of adult epithelial stem cells must exist to replenish damaged cells, they remain unidentified. Here, we report isolation of a subset of basally located human fallopian tube epithelia (FTE) that lack markers of ciliated (β-tubulin; TUBB4) or secretory (PAX8) differentiated cells. These undifferentiated cells expressed cell surface antigens: epithelial cell adhesion molecule, CD44, and integrin α 6. This FTE subpopulation was fivefold enriched for cells capable of clonal growth and self-renewal suggesting that they contain the FTE stem-like cells (FTESCs). A twofold enrichment of the FTESC was found in the distal compared to the proximal end of the tube. The distal fimbriated end of the fallopian tube is a well-characterized locus for initiation of serous carcinomas. An expansion of the cells expressing markers of FTESC was detected in tubal intraepithelial carcinomas and in fallopian tubes from patients with invasive serous cancer. These findings suggest that FTESC may play a role in the initiation of serous tumors. Characterization of these stem-like cells will provide new insight into how the FTE regenerate, respond to injury, and may initiate cancer.

Yokoyama Y, Yokota M, Futagami M, Mizunuma H
Carcinosarcoma of the fallopian tube: report of four cases and review of literature.
Asia Pac J Clin Oncol. 2012; 8(3):303-11 [PubMed]

AIM: Carcinosarcoma of the fallopian tube is extremely rare and the therapeutic prognosis of this disease is unknown.
METHODS: We report on four new cases of this disease and have reviewed 59 carcinosarcomas of the fallopian tube and analyzed the prognosis with respect to the chosen therapeutic method in order to explore the most appropriate therapy.
RESULTS: Out of the 59 patients reviewed, the prognosis was examined in 51 patients that allowed it to be tracked. The 3-year survival rates were 63% for the 27 stage I/II patients and 40% for the 24 stage III/IV patients. The 3-year survival rates were 36% for the 14 surgery-alone patients, 59% for the 13 radiation therapy following surgery patients, 54% for the 27 chemotherapy following surgery patients (the chemotherapy group) and 100% in for the four chemoradiotherapy following surgery patients. A significant difference was observed between the surgery-alone and the chemotherapy groups (Wilcoxon test, P < 0.05), the chemoradiotherapy group demonstrating a better tendency as to survival rate than the surgery-alone group (Wilcoxon test, P = 0.06). Stage III/IV patients accounted for a two-thirds of the chemotherapy group. The 3-year survival rate for all the stage I-IV patients was 63% when a platinum drug was used and 21% when it was not used, suggesting the possibility of extending life through the use of a platinum drug.
CONCLUSION: Chemotherapy using a platinum drug after surgery seems to be most effective treatment in this disease.

Campos SM, Penson RT, Matulonis U, et al.
A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma.
Gynecol Oncol. 2013; 128(2):215-20 [PubMed]

OBJECTIVE: Ovarian cancer is a highly angiogenic tumor and a model for antiangiogenic research. The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways. Sunitinib malate is a multitargeted tyrosine kinase inhibitor. A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib in recurrent ovarian, fallopian tube and peritoneal carcinoma.
METHODS: A nonrandomized phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two. Patients received the study drug at 37.5mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease. Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria. The primary objective of this study was to define the response rate (defined as complete response and partial response) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population.
RESULTS: The response rate (PR+CR) was 8.3% (95% confidence interval: 1.8%, 22.5%). The 16-week and 24 week progression-free survival estimate was 36% (95% confidence interval and 19.2%), respectively. The median progression-free survival estimate was 9.9 weeks. Hypertension and gastrointestional events were the most common toxicities noted.
CONCLUSIONS: A modest response rate of 8.3% was achieved with Sunitinib malate. This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature.

Matulonis UA, Sharma S, Ghamande S, et al.
Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
Gynecol Oncol. 2012; 127(1):63-9 [PubMed]

OBJECTIVES: Aurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or -resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
METHODS: Adult women with malignant, platinum-treated disease received MLN8237 50mg orally twice daily for 7 days plus 14 days' rest (21-day cycles). The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety.
RESULTS: Thirty-one patients with epithelial ovarian (n=25), primary peritoneal (n=5), and fallopian tube carcinomas (n=1) were enrolled. Responses of 6.9-11.1 month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥3 months in 6 (19%). Median PFS and TTP were 1.9 months. Most common drug-related grade≥3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia.
CONCLUSIONS: These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer.

Reyners AK, de Munck L, Erdkamp FL, et al.
A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study.
Ann Oncol. 2012; 23(11):2896-902 [PubMed]

BACKGROUND: In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer.
PATIENTS AND METHODS: In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS).
RESULTS: 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients.
CONCLUSION: Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.

Esselen KM, Rodriguez N, Growdon W, et al.
Patterns of recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with intraperitoneal chemotherapy.
Gynecol Oncol. 2012; 127(1):51-4 [PubMed]

OBJECTIVES: To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy.
METHODS: All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS).
RESULTS: One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p<0.001).
CONCLUSION: Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival.

del Carmen MG, Micha J, Small L, et al.
A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer.
Gynecol Oncol. 2012; 126(3):369-74 [PubMed]

OBJECTIVE: To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer.
METHODS: Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m(2) and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete+partial response]; additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP).
RESULTS: Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4, 83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable) and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6%) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had ≥1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed.
CONCLUSION: Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer.

Watanabe T, Sugino T, Furukawa S, et al.
Malignant mixed Müllerian tumor of the fallopian tube: a case report.
Eur J Gynaecol Oncol. 2012; 33(2):223-6 [PubMed]

Malignant mixed Müllerian tumor (MMMT) of the female genital tract is uncommon and extremely rare in the Fallopian tube. We describe a case of primary MMMT of the Fallopian tube with carcinomatous and heterologous mesenchymal components in a 60-year-old woman. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, pelvic and paraaortic lymph node dissection, and resection of intrapelvic metastases. The tumor formed a large polypoid mass within the right Fallopian tube and had penetrated the wall to the paraovarian space. Microscopic examination revealed two components of poorly differentiated adenocarcinoma and high-grade sarcoma with chondromatous differentiation. The patient received six courses of adjuvant chemotherapy with ifomide and cisplatin and is currently in remission. Although MMMT in the Fallopian tube shows poor prognosis, primary cytoreductive surgery with platinum-based combination chemotherapy may improve survival.

Koskela-Niska V, Riska A, Lyytinen H, et al.
Primary fallopian tube carcinoma risk in users of postmenopausal hormone therapy in Finland.
Gynecol Oncol. 2012; 126(2):241-4 [PubMed]

OBJECTIVE: Primary fallopian tube carcinoma (PFTC) is a rare malignancy and only sparse data exist on its possible association with postmenopausal hormone therapy (HT). We therefore studied this association in a nationwide cohort of Finnish HT users.
METHODS: All women> 50 years using systemic estradiol-only therapy (ET) (n=117,820 hysterectomized women) or estradiol-progestin therapy (EPT) (n=247,781 nonhysterectomized women) for ≥ 6 months during 1994-2008 were identified from the national medical reimbursement register. The incidence of PFTC in HT users was compared to that in the comparable background population (standardized incidence ratio, SIR, with 95% confidence interval, CI).
RESULTS: A total of 160 cases of PFTC were encountered in users of ET (n=34) or EPT (n=126). The use of EPT ≥ 5 years was accompanied by an increased risk for PFTC (SIR 2.15; 95% CI 1.66-2.72). The SIR increased further to 3.36 (95% CI 2.02-5.24) when EPT use lasted ≥ 10 years. The EPT-related risk for PFTC was restricted to the sequential EPT and it was not seen for continuous EPT. Two leading progestins in EPT, norethisterone acetate and medroxyprogesterone acetate, associated with comparable risk elevations. ET use was not associated with the risk for PFTC.
CONCLUSIONS: The long-term, sequential use of EPT associates with an increased risk for PFTC. In absolute terms, 4 additional cases of PFTC would be detected in 10-year follow-up of 10,000 women who have used EPT for at least 5 years.

Terada T
An immunohistochemical study of adenomatoid tumors of the uterus and fallopian tube.
Appl Immunohistochem Mol Morphol. 2012; 20(2):173-6 [PubMed]

Immunohistochemical studies of adenomatoid tumor (AT) are rare in the English literature. The author reports herein immunoprofile of AT of the female genital organs. The materials are 4 cases of AT of the uterus and 1 case of AT of the fallopian tube. The ages of the patients were 37, 41, 43, 45, and 56 years. The sizes of ATs were 0.8 cm, 1 cm, 1.5 cm, 2 cm, and 4 cm. The 4 ATs of the uterus were composed of tubules and smooth muscles, whereas 1 AT of the fallopian tube was composed only of tubules. Immunohistochemically, the ATs were consistently positive for pancytokeratin AE1/3+++, pancytokeratin CAM5.2 ++, cytokeratin (CK) 7 +++, CK8 +, CK18++, CK19++, calretinin +++, and D2-40 ++. Estrogen receptor (ER) and progesterone receptor (PgR) was positive in 4 of 5 cases. CK34βE12 was positive in 1 of 5 case. The Ki-67 labeling ranged from 0.2% to 3%. The smooth muscles in uterine ATs were positive for α-smooth muscle actin, ER, and PgR. The ATs were consistently negative for CK5/6, CK14, CK20, EMA, HMB45, vimentin, desmin, CD31, CD34, factor VIII-relatedantigen, S100 protein, p53, CD68, CDK4, MDM2, and Ber-EP4. These data indicate that ATs consistently express pancytokeratin AE1/3, pancytokeratin CAM5.2, CK7, CK8, CK18, CK19, calretinin, and D2-40, that some ATs express CK34βE12, ER, and PgR, that ATs show little proliferative activity, and that ATs were consistently negative for CK5/6, CK14, CK20, EMA, HMB45, vimentin, desmin, CD31, CD34, factor VIII-related antigen, S100 protein, p53, CD68, CDK4, MDM2, and Ber-EP4.

Aghajanian C, Blank SV, Goff BA, et al.
OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.
J Clin Oncol. 2012; 30(17):2039-45 [PubMed]

PURPOSE: This randomized, multicenter, blinded, placebo-controlled phase III trial tested the efficacy and safety of bevacizumab (BV) with gemcitabine and carboplatin (GC) compared with GC in platinum-sensitive recurrent ovarian, primary peritoneal, or fallopian tube cancer (ROC).
PATIENTS AND METHODS: Patients with platinum-sensitive ROC (recurrence ≥ 6 months after front-line platinum-based therapy) and measurable disease were randomly assigned to GC plus either BV or placebo (PL) for six to 10 cycles. BV or PL, respectively, was then continued until disease progression. The primary end point was progression-free survival (PFS) by RECIST; secondary end points were objective response rate, duration of response (DOR), overall survival, and safety.
RESULTS: Overall, 484 patients were randomly assigned. PFS for the BV arm was superior to that for the PL arm (hazard ratio [HR], 0.484; 95% CI, 0.388 to 0.605; log-rank P < .0001); median PFS was 12.4 v 8.4 months, respectively. The objective response rate (78.5% v 57.4%; P < .0001) and DOR (10.4 v 7.4 months; HR, 0.534; 95% CI, 0.408 to 0.698) were significantly improved with the addition of BV. No new safety concerns were noted. Grade 3 or higher hypertension (17.4% v < 1%) and proteinuria (8.5% v < 1%) occurred more frequently in the BV arm. The rates of neutropenia and febrile neutropenia were similar in both arms. Two patients in the BV arm experienced GI perforation after study treatment discontinuation.
CONCLUSION: GC plus BV followed by BV until progression resulted in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC.

Suprasert P, Cheewakriangkrai C, Manopunya M
Outcome of single agent generic gemcitabine in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma.
Asian Pac J Cancer Prev. 2012; 13(2):517-20 [PubMed]

Single original gemcitabine is commonly used as salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, efficacy data fro this regimen are limited. We therefore conducted a retrospective study to evaluate the outcome of patients who received single-agent generic gemcitabine (GEMITA) after development of clinical platinum resistance. The study period was between May 2008 and December 2010. Gemcitabine was administered intravenously in two different schedules: 1,000 mg/m2 on day 1,8, and 15 every 28 days; and on days 1 and 8 every 21 days with the same dosage. Administration was until disease progression was noted. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG ) criteria while toxicity was evaluated according to WHO criteria. Sixty-six patients met the inclusion criteria in the study period. Two-thirds of them received gemcitabine as the second and third line regimen. The overall response rate was 12.1%. The median progression free survival and overall survival was 2 and 10 months, respectively. With the total 550 courses of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 1.5%; leukopenia, 13.7%; neutropenia, 27.3%; and thrombocytopenia, 3.0%. In conclusion, single agent generic gemcitabine revealed a modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

Dhillon S
Bevacizumab combination therapy: for the first-line treatment of advanced epithelial ovarian, fallopian tube or primary peritoneal cancer.
Drugs. 2012; 72(7):917-30 [PubMed]

Bevacizumab is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumour angiogenesis. In two pivotal, well designed, phase III, clinical trials (GOG-0218 and ICON7) in women with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer, first-line treatment with bevacizumab in combination with standard chemotherapy (carboplatin plus paclitaxel) followed by maintenance treatment with bevacizumab alone significantly prolonged progression-free survival relative to standard chemotherapy. A subgroup analysis of ICON7 suggested that bevacizumab therapy may also be beneficial in patients at high risk of disease progression. In GOG-0218, health-related quality of life (HR-QOL) deteriorated temporarily (during the chemotherapy phase) and slightly, although statistically significantly, with bevacizumab in combination with standard chemotherapy followed by bevacizumab maintenance relative to standard chemotherapy plus placebo maintenance. In ICON7, HR-QOL did not differ to a clinically significant extent between patients receiving bevacizumab plus standard chemotherapy followed by bevacizumab maintenance and those receiving standard chemotherapy alone. Bevacizumab combination therapy had generally acceptable tolerability in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumours.

Gold MA, Brady WE, Lankes HA, et al.
A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
Gynecol Oncol. 2012; 125(3):635-9 [PubMed]

PURPOSE: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC).
PATIENTS AND METHODS: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated.
RESULTS: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p=0.342).
CONCLUSION: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

Barlin JN, Dao F, Zgheib NB, et al.
Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer.
Gynecol Oncol. 2012; 125(3):621-4 [PubMed]

OBJECTIVE: GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen.
METHODS: Using a prospectively maintained database, we evaluated the outcomes of patients who underwent primary optimal cytoreduction for stage III ovarian, tubal, or peritoneal carcinoma followed by IV/IP chemotherapy from 1/05-3/09. Our modified regimen was as follows: IV paclitaxel (135 mg/m(2)) over 3h on day 1, IP cisplatin (75 mg/m(2)) on day 2, and IP paclitaxel (60 mg/m(2)) on day 8, given every 21 days for 6 cycles.
RESULTS: We identified 102 patients who initiated the modified IV/IP regimen and completed chemotherapy. The median follow-up was 43 months. The median age at diagnosis was 57 years (range, 23-76). Primary disease site was: ovary, 77 (75%); fallopian tube, 13 (13%); peritoneum, 12 (12%). FIGO stage was: IIIA, 8 (8%); IIIB, 4 (4%); IIIC, 90 (88%). Residual disease after cytoreduction was: none, 58 (57%); ≤ 1 cm, 44 (43%). The most frequent grade 3/4 toxicities were: neutropenia, 12 (12%); gastrointestinal, 8 (8%); neurologic, 6 (6%). Eighty-two (80%) of 102 patients completed 4 or more cycles of IV/IP therapy; 56 (55%) completed all 6 cycles. The median PFS and OS were 29 and 67 months, respectively.
CONCLUSIONS: By modifying the GOG 172 treatment regimen, convenience, toxicity, and tolerability appear improved, with survival outcomes similar to those of GOG 172. This modified IV/IP regimen warrants further study.

Saha A, Varughese M, Gallagher CJ, et al.
Primary chemotherapy for inoperable ovarian, fallopian tube, or primary peritoneal cancer with or without delayed debulking surgery.
Int J Gynecol Cancer. 2012; 22(4):566-72 [PubMed]

OBJECTIVE: To describe the outcome of primary chemotherapy for women with advanced-stage epithelial ovarian or primary peritoneal cancer and delayed surgery when optimal debulking surgery cannot be achieved at diagnosis.
METHODS: Between 1998 and 2006, we retrospectively reviewed the overall survival and examined prognostic markers in consecutive patients who were not suitable for initial radical surgery because of the extent of disease and/or poor performance status. They were treated with a policy of primary platinum-based chemotherapy, followed whenever possible in responding patients by debulking surgery.
RESULTS: A total of 171 patients received least one cycle of chemotherapy. Eighty-six patients proceeded to surgery and 53 (31% of 171 and 62% of 86) had optimal (<1 cm) residual disease. Eighty-five patients did not undergo surgery because they remained unfit or had not responded sufficiently to chemotherapy. The median overall survival was 18.7 months (95% confidence interval [CI], 16.5-24.2). The median OS in the surgical group for optimal and suboptimal surgery was 40.8 (95% CI, 32.5-50.0) and 22.5 (95% CI, 17.7-37.1) months (P = 0.005). On multivariate analysis, interval surgery and optimal surgery were the only independent prognostic factors (hazard ratios, 0.45 and 0.43, respectively; P = 0.009). In the nonsurgical group, CA125 response was an independent prognostic factor (hazard ratio, 0.34; P = 0.001) with an OS of 21.7 months (95% CI, 14.0-35.4) in women with a normal CA125 after treatment compared with 6.7 (95% CI, 4.5-7.8) months.
CONCLUSIONS: In one third of the women, the tumor was optimally debulked after primary chemotherapy and their median survival was 40.8 months. Suboptimal debulking surgery after primary chemotherapy did not result in a better survival than that achieved after a chemotherapy response alone, suggesting that surgery may be avoided when imaging after chemotherapy demonstrates residual disease that cannot be optimally debulked.

Stewart CJ, Leung YC, Whitehouse A
Fallopian tube metastases of non-gynaecological origin: a series of 20 cases emphasizing patterns of involvement including intra-epithelial spread.
Histopathology. 2012; 60(6B):E106-14 [PubMed]

AIMS:   To determine the frequency and distribution of Fallopian tube involvement in patients with ovarian metastases of non-gynaecological origin.
METHODS AND RESULTS:   All Fallopian tube tissue was processed for histological examination in a consecutive series of 31 patients with ovarian metastases of non-gynaecological origin. The most common primary sites were appendix (n = 10) colon (n = 7), stomach (n = 6) and breast (n = 4). Twenty cases (65%) showed at least one type of tubal spread. Mural involvement was most common (14 cases) but serosal, intra-vascular, intra-epithelial and intra-lumenal spread were also identified in 12, 9, 8 and 11 cases respectively. Intra-epithelial involvement was restricted to the fimbrial epithelium and mimicked tubal carcinoma in situ (CIS) architecturally. Pagetoid invasion was noted in two of the cases.
CONCLUSIONS:   The Fallopian tubes are commonly involved in patients who have neoplasms metastatic to the ovaries. Metastases may show a CIS-like pattern of intra-epithelial spread and therefore small serous CIS-type lesions may not represent proof of tubal tumour origin in patients who have high-stage pelvic serous carcinomas. The frequency of intra-lumenal tumour cells supports transtubal spread as a likely mechanism for mucosal involvement by metastatic tumours involving the lower genital tract.

Noguera IR, Sun CC, Broaddus RR, et al.
Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant low-grade serous carcinoma of the ovary, peritoneum, or fallopian tube.
Gynecol Oncol. 2012; 125(3):640-5 [PubMed]

OBJECTIVE: To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low-grade serous carcinoma (LGSC) of the ovary, peritoneum, or fallopian tube.
METHODS: This open-label, single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease, had received up to 4 platinum- and/or taxane-containing chemotherapy regimens, and had been previously screened for at least one imatinib targeted biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-β, or bcr-abl). Imatinib (600 mg) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression.
RESULTS: Thirteen patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for response. A total of 17 courses were administered (median, 1 course; range, 1-5 courses). Complete or partial responses were not observed. One patient had stable disease for 7.3 months. c-Kit, bcr-abl, or PDGFR-β were present in 48%, 77%, and 100% of patients, respectively. No correlation between best response (stable disease) and the presence of imatinib-targeted biomarkers was observed. Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed. The median progression-free survival time was 1.3 months (95% CI, 1.27, 1.40 months), and the median overall survival time was 14.9 months (95% CI, 11.0, 18.9 months).
CONCLUSION: Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.