A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma.

OBJECTIVES: The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. METHODS: This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20mg/m(2) intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). RESULTS: 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24+weeks [clinical benefit rate 23% (95% CI=9.77%-46.71%)]. Median PFS was 8.4 weeks (95% CI=6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p=0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). CONCLUSIONS: Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.

Phase I trial of erlotinib combined with cisplatin and radiotherapy for patients with locally advanced cervical squamous cell cancer.

PURPOSE: This phase I trial was aimed to determine the maximum tolerated dose and related toxicity of erlotinib (E) when administered concurrently with standard chemoradiation (CRT) for cervical cancer. EXPERIMENTAL DESIGN: In a modified Fibonacci design, the study aimed to study three cohorts of at least three patients receiving escalating doses of erlotinib (50/100/150 mg) combined with cisplatin (40 mg/m(2), weekly, 5 cycles) and radiotherapy (external beam 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in squamous cell cervical carcinoma patients, stage IIB to IIIB. RESULTS: Fifteen patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100 mg, and 8 at DL 150 mg. Patients presented median age 47 (36-59), stage IIB (46.2%) and IIIB (53.8%). Overall, E+CRT was well-tolerated. Three patients did not complete the planned schedule. One patient at DL 100 mg withdrew informed consent due to grade 2 rash; at DL 150 mg, 1 patient presented Raynaud's Syndrome and had C interrupted, and another patient presented grade 4 hepatotoxicity. The latter was interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not lead to limiting in-field toxicity. CONCLUSIONS: E+CRT is feasible to locally advanced squamous cell cervical cancer and is well tolerated. The maximum tolerated dose has been defined as 150 mg. To the best of our knowledge, this is the first report of a combination of erlotinib, cisplatin, and pelvic radiotherapy.