Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study.

INTRODUCTION: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab. METHODS: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240. RESULTS: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain. DISCUSSION: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

A phase II trial of paclitaxel and carboplatin in women with advanced or recurrent uterine carcinosarcoma.

BACKGROUND: Systemic therapy for advanced uterine carcinosarcoma (CS) has been disappointing. The most widely studied regimen is ifosfamide and cisplatinum. Moderate success has been documented using paclitaxel in ovarian CS. The purpose of this study was to evaluate carboplatin/paclitaxel in advanced and recurrent uterine CS. METHODS: A single-arm, prospective, phase II trial opened in October 2001. Primary end points were time to progression (TTP) and response rate (RR). Quality-of-life data were obtained. Patients treated adjuvantly received 6 cycles of carboplatin/paclitaxel every 21 days. Patients with disease at study entry were treated until response, progression, or toxicity. RESULTS: Of 23 patients enrolled, 9 received adjuvant treatment, 13 had documented disease, 1 was inevaluable. Eight of 13 patients with measurable disease had a complete or partial response (62% RR). Overall, median TTP was 9.5 months. In the adjuvant group, median TTP was 15 months. With measurable disease, median TTP was 7.9 months. Median overall survival was 21.1 months. There was no difference in survival between patients with or without measurable disease. For patients having prior radiation, median TTP with recurrence in the radiated field was 13.3 months, and 14.5 months if outside the field (P = 0.71). Two patients (9%) had treatment-limiting toxicity. Quality-of-life scores improved from baseline over time. CONCLUSIONS: Carboplatin and paclitaxel have improved tolerability and RR (62%) compared with previous reports of ifosfamide/cisplatin or ifosfamide/paclitaxel in treating uterine CS. This regimen seems promising and should be considered in combined therapies with targeted agents.