Social determinants of health in uterine carcinosarcoma.

OBJECTIVE: UCS survival outcome disparities by race have been reported. We aimed to investigate social determinants of health (SDOH) and their relation to survival outcomes in women at two affiliated high-volume institutions serving a racially and economically diverse population. METHODS: Women diagnosed with stage I-IV UCS treated at St. Paul University Hospital, University of Texas Southwestern (UTSW) Zale Lipshy Pavilion-William P. Clements Jr. University Hospital, and Parkland Memorial Hospital between 1992 and 2022 were eligible. Patients were identified by the local tumor registries; a retrospective study was conducted. The Pearson chi-square test was utilized for categorical variables. OS and PFS were calculated using Kaplan-Meier estimates and compared with the log-rank test. Multivariate Cox models were used to identify independent prognostic factors. All statistical analyses were performed using SAS, version 9.4. RESULTS: Over half of the 218 patients with UCS were NHB. 35% of the patients had stage IV disease. Most HSP and NHB patients had a lower median household income* than Asian/Pacific Islander (API) or NHW (p < 0.001). Stage at diagnosis significantly affected OS (p < 0.001) but not PFS (p = 0.46) in univariate analyses. Accounting for age at diagnosis, insurance, income*, hospital, distance between hospital and home, months from diagnosis to first treatment, stage, and adjuvant therapy, race was significant for OS (p = 0.03) and PFS (p = 0.04). *Median household income by ZIP Code. CONCLUSIONS: Racial disparities were seen in median household income. Most SDOH independently analyzed in this study did not affect OS. The complex interaction between race and stage in UCS survival outcomes needs further investigation.

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice.

PURPOSE: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. PATIENTS AND METHODS: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. RESULTS: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. CONCLUSION: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC. CLINICALTRIALS: GOV: NCT03517449.

Tumor Treating Fields (TTFields) Therapy Concomitant with Taxanes for Cancer Treatment.

Non-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug-drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient's skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers.

Stage IVA cervical cancer: outcomes of disease related complications and treatment.

INTRODUCTION: Stage IVA cervical cancer is an uncommon diagnosis. The course of the disease and the complications of treatment are not well characterized. The goal of this study was to report treatment outcomes of patients with stage IVA cervical cancer. METHODS: A single institution retrospective review was carried out of all patients treated for stage IVA cervical cancer from January 2008 to July 2017. Patients were clinically staged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria for cervical cancer. Inclusion criteria were patients with stage IVA cervical cancer of any histologic subtype, including patients with evidence of para-aortic lymph node involvement, treated at the institution during this time period. Overall survival and progression free survival were calculated using the Kaplan-Meyer method. Comparisons between survival were done using the Cox proportional hazards regression model and the log rank test. RESULTS: We identified 25 patients with stage IVA cervical cancer. Mean age at diagnosis was 54 years (range 27-77). Squamous cell carcinoma was the histologic diagnosis in 24 of 25 patients (96%), with 1 case of small cell carcinoma (4%). 21 patients completed a full course of radiation. The median overall survival for patients who completed their treatment was 60 months (range 3-136), with a 2 year overall survival of 63%. The median progression free survival was 27 months (range 0-125), with a 2 year progression free survival of 40%. 11 of 25 patients (44%) developed fistulas during the course of their disease, and 55% of these were complex fistulas. 19 of 25 (76%) patients had a percutaneous nephrostomy for either hydronephrosis or diversion of vesicovaginal fistula. 111 unplanned admissions occurred among the 25 patients, and infections of the urinary tract was implicated in 46 (41%) of these. The cohort had a total of 92 emergency department visits, with pain control (36%) and medication refills (15%) being the most common presentations. DISCUSSION: Patients with stage IVA cervical cancer may have substantial long term survival, although the sequelae of disease and treatment is associated with significant morbidity. Symptoms of fistula, percutaneous nephrostomy complications, and chronic pain present unique issues that require extensive supportive care.

Phase II study of intraperitoneal submicron particle paclitaxel (SPP) plus IV carboplatin and paclitaxel in patients with epithelial ovarian cancersurgery.

Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. This study compared two dose-levels of SPP instilled into the peritoneal cavity (IP) in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment emergent adverse events. Clinical response was determined by symptoms, physical exams, CT scans, and serum CA-125 measurements. Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m2 and three received 200 mg/m2. Seven subjects completed the 12-month follow-up period. Six patients were evaluable due to one subject who had unevaluable scans throughout the follow-up period and was thus excluded from PFS determination. Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas.

Progress in endometrial cancer: Contributions of the former Gynecologic Oncology Group.

For over forty years, the Gynecologic Oncology Group drove progress in treating endometrial cancer. The first decades of investigation began with a meticulous prospective, surgicopathologic staging study that was the platform for development of all subsequent trials. The resultant statistical model of low risk, intermediate risk, and high-risk groups of patients led to trials where therapeutic modalities were best targeted at disease spread. A clear role for chemotherapy was established. It was realized that greater advances might be achieved with the advent of newer anti-neoplastic agents and these agents were subjected to extensive phase II testing. These agents later were integrated into comparison trials for advanced endometrial cancer. Multimodality therapy continues to show promise. Hormonal therapy was thoroughly investigated and led to combination hormonal therapy trials. Newer agents, including biologics are under active study, as well as the potential contribution of modern imaging techniques. Finally, GOG0210 established a repository of clinical specimens with detailed clinical and epidemiologic data from patients with surgically staged endometrial carcinoma. This should provide for a much greater understanding of molecular characteristics associated with risk of endometrial cancer recurrence, clinical and histological characteristics, and epidemiologic factors.

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial.

BACKGROUND: Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5-9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy. METHODS: QUADRA was a multicentre, open-label, single-arm, phase 2 study that evaluated the safety and activity of niraparib in adult patients (≥18 years) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with three or more previous chemotherapy regimens. The study was done in the USA and Canada, and 56 sites screened patients (50 sites treated at least one patient). Patients received oral niraparib 300 mg once daily continuously, beginning on day 1 and every cycle (28 days) thereafter until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with homologous recombination deficiency (HRD)-positive tumours (including patients with BRCA and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous anticancer therapy regimens (primary efficacy population). Efficacy analyses were additionally done in all dosed patients with measurable disease at baseline. FINDINGS: Between April 1, 2015 and Nov 1, 2017, we screened 729 patients for eligibility and enrolled 463 patients, who were initiated on niraparib therapy. At the time of database lock (April 11, 2018), enrolment had closed and the study was ongoing, with 21 patients still on treatment. Patients had received a median of four (IQR 3-5) previous lines of therapy, and the median follow-up for overall survival was 12·2 months (IQR 3·7-22·1). 151 (33%) of 463 patients were resistant and 161 (35%) of 463 patients were refractory to the last administered platinum therapy. 13 (28%) of 47 patients in the primary efficacy population achieved an overall response according to RECIST (95% CI 15·6-42·6; one-sided p=0·00053). The most common drug-related grade 3 or worse treatment-emergent adverse events were anaemia (113 [24%] of 463 patients) and thrombocytopenia (95 [21%] of 463 patients). The most common treatment-emergent serious adverse events were small intestinal obstruction (34 [7%] of 463 patients), thrombocytopenia (34 [7%] of 463 patients), and vomiting (27 [6%] of 463 patients). One death due to gastric haemorrhage was considered treatment related. INTERPRETATION: We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. FUNDING: Tesaro.

New therapies for advanced, recurrent, and metastatic endometrial cancers.

Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were diagnosed with endometrial cancer, and approximately 11,000 died from this disease. From 1987 to 2008, there was a 50% increase in the incidence of endometrial cancer, with an approximate 300% increase in the number of associated deaths. Although there are many chemotherapeutic and targeted therapy agents approved for ovarian, fallopian tube and primary peritoneal cancers, since the 1971 approval of megestrol acetate for the palliative treatment of advanced endometrial cancer, only pembrolizumab has been Food and Drug Administration (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer; this highlights the need for new therapies to treat advanced, recurrent, metastatic endometrial cancer. In this review, we discuss current and emerging treatment options for endometrial cancer, including chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute (NCI) and others are now focusing their efforts on the design of scientifically rational targeted therapy and immunotherapy trials for specific molecular phenotypes of endometrial cancer. This is essential for the advancement of cancer care for women, which is threatened by a severe enrollment decline of approximately 80% for gynecologic oncology clinical trials.

Surgical and systemic management of endometrial cancer: an international survey.

PURPOSE: To ascertain the spectrum of clinical management of endometrial carcinoma (EC) the largest international survey was conducted to evaluate and identify differences worldwide. METHODS: After validation of a 15-item questionnaire regarding surgical and adjuvant treatment of EC in Germany, an English-adapted questionnaire was put online and posted to all the major gynecological cancer Societies worldwide for further distribution commencing in 2010 and continued for 26 months. RESULTS: A total of 618 Institutions around the world participated: Central Europe (CE), Southern Europe (SE), Northern Europe (NE), Asia and USA/Canada/UK. Both a therapeutic and staging value was attributed to systematic pelvic and paraaortic lymph node dissection (LND) in CE (74.6%) and in Asia (67.2%), as opposed to USA/UK where LND was mainly for staging purposes (53.5%; p < 0.001). LND was performed up to the renal veins in CE in 86.8%, in Asia in 80.8%, in USA/UK in 51.2% and in SE in 45.1% (p < 0.001) of cases. In advanced disease, centers from Asia were treated most with adjuvant chemotherapy alone (93.6%), as opposed to centers in SE, CE and UK/USA that employed combination chemo-radiotherapy in 90.9% (p < 0.001) of cases. Paclitaxel/carboplatin was mostly used followed by doxorubicin/cisplatin (75 vs. 23.3%; p < 0.001). In total, 94% of all participants supported the concept of treating EC patients within appropriate clinical trials. CONCLUSIONS: There is broad range in both the surgical and adjuvant treatment of EC across different countries. Large-scale multicenter prospective trials are warranted to establish consistent, evidence-based guidelines to optimize treatment worldwide.

Pemetrexed and cisplatin for the treatment of advanced, persistent, or recurrent carcinoma of the cervix: a limited access phase II trial of the gynecologic oncology group.

PURPOSE: To estimate the antitumor activity of pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, this study will determine the effects of this regimen on progression-free survival and overall survival. PATIENTS AND METHODS: Eligible, consenting patients received pemetrexed 500 mg/m(2) and cisplatin 50 mg/m(2) intravenously repeated every 21 days until disease progression or adverse events prohibited further therapy. Patients received no prior therapeutic chemotherapy, except when administered concurrently with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with Common Terminology Criteria for Adverse Events v 3.0. The primary measure of efficacy was tumor response according to Response Evaluation Criteria in Solid Tumors. The study was stratified by prior radiation therapy. RESULTS: From September 2008 to November 2011, 55 patients were enrolled by five Gynecologic Oncology Group member institutions; of those, 54 patients were eligible and assessable. The regimen was well tolerated with 26% receiving more than nine cycles. The most common greater than grade 2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial). The median progression-free survival was 5.7 months, and overall survival was 12.3 months. CONCLUSION: Pemetrexed in combination with cisplatin demonstrates activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix.

A phase II evaluation of pemetrexed (Alimta, LY231514, IND #40061) in the treatment of recurrent or persistent endometrial carcinoma: a phase II study of the Gynecologic Oncology.

OBJECTIVE: To estimate the anti-tumor activity of pemetrexed in patients with advanced or recurrent carcinoma of the endometrium and to determine the nature and degree of toxicity. METHODS: A multicenter phase II trial was conducted by the Gynecologic Oncology Group (GOG). Patients must have had advanced or recurrent measurable carcinoma of the endometrium and failed one prior chemotherapy regimen. Pemetrexed at a dose of 900 mg/m(2) was administered as an IV infusion over 10 min every 21 days. RESULTS: From May 1, 2006 to July 31, 2007, 27 patients were entered by 10 member institutions of the GOG with two patients being deemed ineligible. A total of 101 cycles were administered with 28% of patients receiving five or more cycles. Overall, the treatment was well tolerated. More serious toxicities (grade 3 and 4) included anemia in 20%, leukopenia in 40%, neutropenia in 48%, and constitutional in 16%. No treatment-related deaths were reported. One patient (4%) had a partial response. Eleven patients (44%) had stable disease and eleven (44%) patients had increasing disease. Response could not be assessed in two patients (7%). Median progression-free survival was 2.7 months and overall survival was 9.4 months. CONCLUSION: Pemetrexed has minimal activity in the treatment of recurrent or persistent endometrial carcinoma at the dose and schedule tested.

Pharmacotherapy of endometrial cancer.

BACKGROUND: Endometrial cancer is the seventh most common malignancy among women worldwide. Despite most cases being diagnosed at an early stage, the death rate has increased steadily over the past 20 years. The lack of an effective, standardized adjuvant treatment for women at a high risk of recurrence has contributed to these disappointing results. OBJECTIVES: The goal of this review was to assess the role of hormonal and cytotoxic therapies in the adjuvant treatment of endometrial cancer. Once defined, an evidence-based management algorithm for this neoplasm was proposed. METHODS: A thorough literature search was undertaken using the Cochrane and Pubmed databases. Systematic reviews, meta-analyses, and randomized controlled trials were first collected and critically analyzed. Other study types were secondarily considered when pertinent. CONCLUSIONS: The choice of the adjuvant therapy in early-stage endometrial cancer must be a patient-specific decision. Preliminary data suggest a role for chemotherapy in high-risk subgroups. However, further research is necessary to confirm this. To date, hormonal therapy has not been widely used in the management of early-stage disease, other than for conservative treatment in a fertility-sparing setting. Both hormonal and chemotherapy represent valuable therapeutic tools for the management of patients affected by advanced disease.

Recent progress: gynecologic oncology group trials in uterine corpus tumors.

The Gynecologic Oncology Group (GOG) has conducted multiple trials related to neoplasms of the uterine corpus. Recently, several of these trials have been presented and/or published. Areas of focus included the feasibility of laparoscopic staging for endometrial cancer, the adjuvant management of locally advanced endometrial cancer, whole abdominal irradiation in maximally resected advanced endometrial carcinoma, and combination chemotherapy regimens for stage I and II carcinosarcoma after primary surgery and for advanced or recurrent carcinosarcoma. This article will discuss the background and details of each of these important advances.

Chemo- and radiotherapy in adjuvant management of optimally debulked endometrial cancer.

The role of chemotherapy and radiotherapy in adjuvant management of optimally debulked endometrial cancer with extrauterine involvement is evolving. Recent studies have suggested an expanded role for chemotherapy and questioned the benefit of radiation therapy. Ongoing and planned clinical trials should provide clarification.

Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group.

OBJECTIVE: To estimate the anti-tumor activity of pemetrexed in patients with advanced or recurrent carcinoma of the cervix that failed on higher priority treatment protocols and to determine the nature and degree of toxicity. METHODS: A multicenter Phase II trial was conducted by the Gynecologic Oncology Group (GOG). Patients must have had advanced or recurrent measurable carcinoma of the cervix, and failed one prior chemotherapy regimen. Pemetrexed at a dose of 900 mg/m(2) was to be administered as an IV infusion over 10 min every 21 days. RESULTS: From July 6, 2004 to April 3, 2006, twenty-nine patients were entered by ten member institutions of the GOG. Two patients did not receive treatment and thus were inevaluable. A total of 128 cycles were administered with 37% of patients receiving six or more cycles. The treatment was well tolerated overall. More serious toxicities (grade 3 and 4) included anemia in 41%, leukopenia in 30%, neutropenia in 26%, and infection in 26%. No treatment related deaths were reported. Four patients (15%) had partial responses with a median response duration of 4.4 months. The response rate for non-radiated or radiated disease sites was 25% and 7% respectively. Sixteen patients (59%) had stable disease and seven (26%) patients had increasing disease. Median progression free survival (PFS) was 3.1 months and overall survival (OS) was 7.4 months. CONCLUSION: Pemetrexed at this dose and schedule showed moderate activity against advanced or recurrent cervical cancer that has failed prior chemotherapy. Data from other tumor sites has suggested synergy between pemetrexed and cisplatin and should be considered for further study.

Gynecologic oncology group trials in uterine corpus malignancies: recent progress.

The Gynecologic Oncology Group (GOG) has conducted multiple trials related to malignancies of the uterine corpus. Recently, several of these trials have been presented and/or published. Areas of focus included the feasibility of laparoscopic staging for endometrial cancer, the adjuvant management of locally advanced endometrial cancer, whole abdominal irradiation in maximally resected advanced endometrial carcinoma, and combination chemotherapy regimens for stage I and II carcinosarcoma after primary surgery and for advanced or recurrent carcinosarcoma. This article will discuss the background and details of each of these important advances.

Hormonal therapy in epithelial ovarian cancer.

The ovary is an endocrine and end organ. Hormones and their receptors have been associated with ovarian cancer and may be related to its causation. Some data suggest that hormonal therapies may have an effect on ovarian cancer in palliative settings. The most well studied anticancer drugs are tamoxifen, megestrol acetate, medroxyprogesterone acetate, leuprolide acetate, anastrozole and letrozole. Presently, no hormonal therapy is approved by the US FDA for the treatment of any type of ovarian malignancy or is listed as an active agent by any of the authoritative compendia. Owing to the endocrine associations with ovarian cancer, the minimal side effects of hormonal therapy and the demonstrated activity of hormonal therapies in other endocrine organ-associated malignancies, further study of hormonal therapies for ovarian cancer is warranted.

Phase II evaluation of topotecan in carcinosarcoma of the uterus: a Gynecologic Oncology Group study.

OBJECTIVES: To estimate the antitumor activity of topotecan in patients with persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the uterus and to determine the nature and degree of toxicity of topotecan in this cohort of patients. MATERIALS AND METHODS: Eligible patients had measurable advanced or recurrent carcinosarcoma of the uterus. Topotecan at a target dose of 1.5 mg/m(2) was administered IV daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. RESULTS: Twenty-seven member institutions entered 51 patients. Of the patients entered, 48 were eligible. Patient characteristics included a median age of 65, with 33% having prior radiation and 92% having prior chemotherapy. Twenty-six patients (54%) had a performance status (PS) of 0, 18 (38%) had a PS of 1, and four (8%) had a PS of 2. Patients received from 1 to 21 (with a median of 2) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 35 (73%) patients, leukopenia in 14 (29%), and thrombocytopenia in 10 (21%). Three (6%) patients developed neutropenic sepsis and died shortly after their first treatment cycle. There were five (10%) complete responses; 13 (27%) patients maintained stable disease, 26 (54%) experienced increasing disease, and reassessment did not occur in four (8%). CONCLUSION: Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent uterine carcinosarcoma previously treated with chemotherapy.

Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study.

PURPOSE: A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of capecitabine in women with measurable platinum-sensitive ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities. EXPERIMENTAL DESIGN: Patients were treated with a daily starting dose of 2500 mg/m2/day (divided in two doses given every 12 h) for 14 days of each 21-day cycle. Genotyping in the 5' and 3' ends of TS was performed in DNA from 23/23 pre-treatment blood specimens. Relative gene expression of TS, DPD, and TP was quantified in 18/21 paraffin-embedded tumor specimens. RESULTS: Of the 27 patients enrolled on study, 2 were never treated leaving 25 patients evaluable. Two patients (8.0%) achieved a partial response, 13 (52%) exhibited stable disease, 5 (20%) displayed increasing disease, and response could not be assessed in 5 (20%). The median time to progression and survival was 3.9 and 21.2 months, respectively. The most common serious toxicities were nausea/vomiting, gastrointestinal, and dermatological. There was one treatment-related death. TS expression was associated with severe nausea/vomiting (P = 0.039), but not with other severe toxicities. TS genotype or expression of DPD or TP was not associated with any of the severe toxicities. CONCLUSIONS: Based on the low response rate, this trial was closed after the first stage of accrual, the drug was not selected for further study in this patient population, and biomarker associations with response could not be assessed.