The aim of this study was to evaluate the activity and toxicity of a tirapazamine (TPZ)/cisplatin drug combination in patients with stage IV or recurrent cervical cancer. The chemotherapy was administered for a maximum of eight cycles every 21 days. TPZ was administered intravenously at 330 mg/m 2 over a 2-h infusion, followed 1 h later by cisplatin intravenously at 75 mg/m 2 over 1 h on day 1. All patients received antiemetics including dexamethasone, ondansetron, and lorazepam. Subsequent doses were unchanged, reduced, or omitted according to observed toxicity and protocol guidelines. Response evaluation was performed every two cycles. Thirty-six patients with stage IV or recurrent cervical cancer were treated. Ninety-four percent of patients had prior radiotherapy. Two patients had prior chemotherapy. There were two complete responses and eight partial responses (27.8%). An additional 11 patients (30.6%) had stable disease as their best response. Response rate was greater in tumors outside of the previously radiated field (44.4% vs 11.1%). The median time to progression was 32.7 weeks. The most frequent grade 3 or 4 adverse events were nausea, vomiting, and fatigue, which occurred in 30.6%, 25%, and 22% of subjects, respectively. Anemia was the most frequent grade 3 or 4 hematologic toxicity at 8.3%. We conclude that the combination of cisplatin and TPZ was reasonably well tolerated in patients with recurrent or advanced cervical cancer. Further evaluation of this drug combination may be warranted.
LBA5007 Background: BEV, a humanized anti-VEGF monoclonal antibody, has shown a progression-free survival (PFS) benefit in 2 frontline phase III trials in patients with EOC, PPC and FTC. The therapeutic impact of BEV in combination with carboplatin (C) and gemcitabine (G) followed by single agent BEV to disease progression (PD) was evaluated in this phase III trial in the platinum-sensitive recurrent setting. Methods: Patients had recurrent, platinum-sensitive EOC, PPC or FTC, 1 prior regimen, no prior BEV, ECOG performance status 0-1, measurable disease. Subjects were randomized to: Arm A: [IV C (AUC 4, Day (D) 1) + G (1,000 mg/m 2 D1 and 8) + placebo (PL) D1] q21D x 6 cycles (c) → PL q21D until PD or unacceptable toxicity (tox) Arm B: [CG + BEV (15 mg/kg) D1] q21D x 6 c → BEV q21D until PD or tox primary endpoint was investigator assessed PFS (RECIST). Secondary endpoints included objective response (OR), overall survival (OS), duration of response and safety. The design provided 80% power to detect a 27% reduction in the hazard of progression or death in Arm B vs A, limiting the overall type I error of 5%. Results: OCEANS enrolled 484 patients (242 per arm) from 4/07 - 1/10, median follow up of 24 months. BEV plus CG followed by single agent BEV to PD significantly increased PFS compared to CG alone (HR=0.484, p<0.0001). OR increased by 21% (p<0.0001). OS data is immature with only 29% of patients having had an event. The safety profile was consistent with other BEV trials. Conclusions: Results show a statistically significant and clinically relevant benefit when bevacizumab is added to chemotherapy in patients with recurrent, platinum sensitive EOC, PPC, and FTC. This is the first phase III trial of an antiangiogenic to demonstrate a clinical benefit to these patients. [Table: see text]
9010 BACKGROUND: We previously reported the activity of gemcitabine plus docetaxel in LMS. Our phase II trial was expanded to include non-LMS histologies. We report the longer-term progression-free (PFS) and overall survival (OS) for LMS, and response rates (RR) for 52 patients with LMS and non-LMS sarcomas. METHODS: From 6/99–4/03, 52 patients with unresectable LMS (n=42) or other sarcoma (n=10) who had failed 0–2 prior chemotherapy regimens were enrolled on a phase II study of gemcitabine 900 mg/m2 IV days 1 and 8, plus docetaxel 100 mg/m2 IV day 8 with GCSF SQ days 9–15, delivered every 21 days for a maximum of 8 on-study cycles. Patients with prior pelvic radiation received 25% lower doses of both agents. Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2, and by 90-minute infusion in all subsequent cycles. Patients were followed until death. RESULTS: Among 52 pts (mean age 54, range 23–77), the mean number of cycles delivered on study was 4.6 (range 1–11). Overall objective RR was 35% (95% confidence interval [95%CI] 22–48%). RR in LMS was 40%, and RR in non-LMS was 10%. Grade 3–4 toxicities were observed in 15% of pts, consisting mostly of myelosuppression. 7% of pts had pulmonary toxicity. PFS among LMS patients at 6 months is 34% (95%CI 20–49%), and OS at 2 years is 47% (95%CI 31–63%). Among the 18 patients with objective responses, median duration of response was 7 months (range 4.1–45 months). CONCLUSION: Gemcitabine plus docetaxel is active in LMS. In non-LMS histologies small numbers preclude firm conclusion about this regimen's activity. A significant minority of LMS patients have relatively prolonged PFS with this regimen. A multi-center study is underway to examine gemcitabine vs. gemcitabine with docetaxel in patients with metastatic soft-tissue sarcoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly; Aventis; Pfizer; Daiichi
The objective of this study was to analyze retrospective populations with recurrent ovarian cancer to assess differences in CA-125 patterns during chemotherapy. The populations included all patients treated between January 1994 and January 2004, who received liposomal doxorubicin and topotecan, and all patients treated between July 1997 and June 2001, who received carboplatin. Prognostic variables were abstracted from the medical records. Eighty-nine patients received liposomal doxorubicin and topotecan therapy and 21 received carboplatin; of these, 59 (liposomal doxorubicin), 60 (topotecan), and 17 (carboplatin) patients had evaluable CA-125 patterns. Patients given liposomal doxorubicin were more likely to have received only one or two cycles of therapy (37/89 [42%]) than patients receiving either carboplatin (5/21 [24%]) or topotecan (20/89[22%]). In cycle 1, CA-125 increases in patients were carboplatin, 4/17 (24%); liposomal doxorubicin, 41/59 (69%); and topotecan, 11/60 (18%). In cycle 2, CA-125 increases were carboplatin, 2/16 (13%); liposomal doxorubicin, 19/37 (51%); and topotecan, 9/50 (18%). In cycle 3, CA-125 increases were carboplatin, 0/12 (0%); liposomal doxorubicin, 7/23 (30%); and topotecan, 6/38 (16%). Of patients having any CA-125 decrease and given two or more cycles, fewer declines were seen in those given liposomal doxorubicin precycle 2 (18/35[51%]) than in those given carboplatin (13/16[81%]) or topotecan (49/56[88%]). The most prominent delay in CA-125 decline was in patients given liposomal doxorubicin compared with those given topotecan or carboplatin. In the entire population, only 3 of 107 (2.8%) patients demonstrated first CA-125 decline precycle 4. Discontinuation of therapy solely on the basis of early CA-125 increase (precycle 3), particularly with liposomal doxorubicin chemotherapy, may exclude some patients who will benefit from continued therapy.
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