Phase II evaluation of capecitabine in refractory nonsquamous cell carcinoma of the cervix: A Gynecologic Oncology Group Study
Department of Obstetrics-Gynecology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.International Journal of Gynecological Cancer (Impact Factor: 1.95). 10/2007; 18(4):773-8. DOI: 10.1111/j.1525-1438.2007.01080.x
We conducted a multi-institutional study to assess the activity and toxicity of capecitabine in patients with persistent or recurrent nonsquamous cancer of the cervix. Eligible patients were required to possess adequate renal, hepatic and bone marrow function and a Gynecologic Oncology Group performance status of 0-2. Histologic confirmation of the original primary cancer was mandated. Patients must have received one prior systemic chemotherapeutic regimen for cervical cancer that did not include the chemotherapy that may have been administered in conjunction with prior radiation therapy. The initial dose schedule was 2500 mg/m2 orally daily in two divided doses for 14 consecutive days, followed by a 7-day rest, such that each cycle was 21 days. Responses were assessed using response evaluation criteria in solid tumors. Twenty-one patients were entered into the trial. One patient was declared ineligible for wrong cell type; thus, 20 were evaluable for toxicity. A median of 2.5 cycles was administered (range 1-11). There was one septic death. Grade 4 neutropenia, renal, neurologic, and pulmonary toxicity was seen in 5%, 5%, 5%, and 10% patients, respectively. There were no responses. Nine patients (45%) each had stable disease and nine showed progression. The remaining two cases (10%) did not have subsequent disease assessment and response could not be assessed. Oral capecitabine at the dose and schedule tested has insignificant activity in nonsquamous cervical cancer patients previously treated with chemotherapy.
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ABSTRACT: This retrospective study evaluates the efficacy and safety of chemotherapy with docetaxel, carboplatin and 5-FU (TCF) in patients with metastatic cervical carcinoma. Between January 2006 and April 2007, 23 patients with metastatic cervical carcinoma were included in the study. Patients fulfilling the following criteria were enrolled: histologically confirmed metastatic cervical carcinoma; documented progressive disease (PD) after cisplatinum-based treatment if applicable; an Eastern Cooperative Oncology Group (ECOG) performance scale of 0-2; not candidates for local therapy; measurable metastatic lesions as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST); and adequate hematologic, hepatic, and renal functions. Treatment consisted of intravenous docetaxel at 60 mg/m(2) diluted in 500 ml 5% glucose administered over 1 h on day 1, followed by carboplatin (AUC of 5 or 6) given as a 1-h intravenous infusion delivered on day 2, followed by 5-FU at 500 mg/m(2) diluted in 500 ml normal saline continuously infusion for 24 h for 2 days on day 2. Chemotherapy was repeated every 21 days, and a total of 1-5 courses were performed. There were 3 (13%) complete responses; 4(17%) partial responses; 6 (26%) with stable disease, and 10 (43%) with disease progression. The overall response rate was 56%. After a median follow-up of 16 months, the median overall survival was 12 months. Neutropenia was the most severe toxicity. The combination of docetaxel, carboplatin and 5-fluorouracil (TCF) appears to have activity in metastatic cervical carcinoma with acceptable toxicity profile.
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ABSTRACT: Platinum-based drugs are the most active agents in cervical carcinoma. The aim of this study was to assess the activity and toxicity of the association of cisplatin and capecitabine as first-line treatment in patients with advanced, persistent, or recurrent carcinoma of the cervix. Patients with histological proven primary carcinoma, presence of measurable tumors, age 18 years or older, performance status of 2 or less, and adequate bone marrow, renal, and hepatic functions were potentially eligible for this trial. Prior chemotherapy was allowed only in the context of radiosensitization. Treatment consisted of 50 mg/m of intravenous cisplatin on day 1 with 2500 mg/m oral capecitabine daily in 2 divided doses for 14 consecutive days in 21-day cycles. Responses were assessed using response evaluation criteria in solid tumors. Between November 2004 and October 2007, 22 women were entered into the trial. Median age was 51 years (range, 37-70 years). Seventeen patients had prior radiotherapy, and 13 received a radiation sensitizer, whereas 2 patients underwent surgery exclusively and 3 patients had no prior treatment. A median of 5 cycles was administered (range, 2-8 cycles). There were one septic death, one grade 4 neutropenia, and one grade 4 anemia. Grade 3 fatigue, gastrointestinal toxicity, renal toxicity, and hand-foot syndrome were seen in 31.8%, 22.7%, 9%, and 9% of the patients, respectively. There were 1 complete response and 6 partial responses for an overall response rate of 31.8%. Seven patients (31.8%) each had stable disease, and 8 patients showed progression. The median time to progression was 7.6 months, with a median overall survival of 20 months. These results seem to suggest that the capecitabine-cisplatin combination is a moderately tolerated and active regimen in advanced, persistent, or recurrent cervical carcinoma patients. Further evaluation of this drug combination may be warranted.
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ABSTRACT: There is a scarcity of outcome data regarding phase 1 trials for patients with gynecologic malignancy. The objective of this study was to assess toxicity, clinical benefit and prognosticators in gynecologic oncology patients participating in phase 1 trials. All phase 1 oncology trials conducted at Albert Einstein Cancer Center from 1999-2010 were reviewed and extracted for relevant demographic and clinical data concerning patients with gynecologic malignancy. Cox-proportional and logistic regression modeling were used for multivariate analysis. 120 distinct patients with gynecologic malignancy participated in 41 trials, constituting 30.6% of all phase 1 patients enrolled in the same time period. The median age is 59 years. Out of the 184 patients enrolled, 160 individual responses were evaluable. Seventeen DLT events (9.2%) occurred, including 1 (0.5%) treatment-related mortality. There were 27.2% ≥ grade 3 hematologic and 24.4% non-hematologic toxicity. Eighty patients had stable disease (SD, 50%), including 21.9% with SD ≥ 4 months, 11 (6.3%) with partial response (PR), and 3 (1.9%) achieving complete response (CR). The clinical benefit rate (CBR=SD + CR + PR) was 58.1%. Albumin (Alb) ≤ 3.5g/dL and abnormal ANC were independent negative prognosticators of survival. We also found a continuous correlation between changes in Albumin (p=0.02) and LDH (p=0.02) and odds of achieving CBR ≥ 4month. Our clinical outcome and safety data suggested that phase 1 trials may be a reasonable option for patients with advanced and recurrent gynecologic cancer. The potential prognosticators identified should be further validated in larger trials.
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