Trial Of Irinotecan In Patients Research Articles

A phase II trial of irinotecan in patients with advanced or recurrent endometrial cancer and correlation with biomarker analysis

ObjectiveChemotherapy for advanced or recurrent endometrial cancer requires further development. Irinotecan hydrochloride (CPT-11) suppresses tumor growth in several endometrial cancer strains. The present study evaluated the anti-tumor activity and toxicity of CPT-11 in patients with advanced or recurrent endometrial cancer. MethodsEnrolled patients had advanced endometrial cancer with measurable lesions and received 2 pretreatment regimens. A 90-minute intravenous infusion of CPT-11 (100 mg/m2) was given on days 1, 8, and 15 of a 4-week cycle, aiming for an effect with ≤2 cycles. Treatment was continued until the primary disease worsened or severe toxicity occurred. The primary endpoint was response rate, and the secondary endpoints were progression-free survival, overall survival, and adverse events. Antitumor effect and adverse events were evaluated according to RECIST version 1.1 and NCI-CTC AE version 3.0, respectively. ResultsTwenty-two patients were registered (11 endometrioid carcinomas and 11 serous carcinomas). The median duration of the treatment-free interval (TFI) was 7.5 months, and the median number of administered cycles per patient was 4. Response rate was 36.4% (complete response: 1 patient, partial response: 7 patients). Clinical benefit rate, including stable disease, was 77.3%. Median progression-free and overall survival was 4.4 and 18.4 months, respectively. Observed adverse events included grade 4 hematotoxicity (neutropenia and thrombocytopenia), and grade 2 or 3 non-hematotoxicity (diarrhea). All adverse events were manageable. Biomarker predictors of therapeutic effectiveness were not observed. ConclusionAs a single agent, CPT-11 has anti-tumor activity for advanced or recurrent endometrial cancer and has manageable adverse events.

Single Agent Irinotecan for the Treatment of Metastatic or Recurrent Squamous Carcinoma of the Head and Neck (SCCHN)

Background Patients with recurrent or metastatic head and neck cancer (HNC) have a poor response and survival with currently available chemotherapy agents. Thus new agents are needed. We report the results of a phase II trial of irinotecan in patients with metastatic or recurrent HNC. Patients and Methods Chemonaive patients were treated with irinotecan 125 mg/m2 on a weekly schedule for four weeks, followed by a two week rest. However, due to excessive toxicity, the dose and schedule of irinotecan was changed to 75 mg/m2 on days 1 and 8 of a 21 day cycle. All previously treated patients received 75 mg/m2 on days 1 and 8 of a 21 day cycle. Results Forty-nine patients were enrolled on study. The response rate was 20% in the chemonaive patients treated at the 125 mg/m2 dose. The response rate decreased to 12.5% at the 75 mg/m2 dose. In the previously treated cohort, the response rate was 20%. Median survival for the chemonaive and previously treated cohorts were 6.7 months and 5.0 months, respectively. Conclusions Irinotecan has modest activity in chemonaive and previously treated HNC, thus it merits further study in this advanced disease population.

A Phase II Trial of Irinotecan in Patients with Previously Untreated Advanced Esophageal and Gastric Adenocarcinoma

Chemotherapy options for esophagogastric adenocarcinoma remain limited. Irinotecan has demonstrated broad activity in a variety of epithelial malignancies. Forty-six patients with previously untreated, measurable, unresectable, or metastatic esophagogastric adenocarcinoma were enrolled. Patients received irinotecan (125 mg/m2 intravenously over 90 min weekly) for 4 consecutive weeks followed by a 2-week rest. Forty-three patients received at least one treatment and were evaluable for response and toxicity. One complete and five partial responses were observed, for an overall response rate of 14% (95% CI, 4-24%). Median survival for all 43 patients was 6.4 months (95% CI, 4.6-8.2 months). Grade 3 to 4 toxicity included 10 patients (23%) with neutropenia, 13 patients (30%) with late diarrhea, 6 patients (14%) with vomiting, and 6 patients (14%) with fatigue. We conclude that although single-agent irinotecan is an active agent for esophagogastric adenocarcinoma, the schedule utilized in this trial is associated with moderate toxicity. When used as a single-agent, a tri-weekly schedule may be preferable for this patient population.