HOUSTON"Cisplatin (Platinol) has served us well, but we need to move on and study combinations with less toxic carboplatin(Drug information on carboplatin) (Paraplatin) or oxalipla-tin in gastric and gastroesophageal junction cancers," Jaffer Ajani, MD, told the clinical investigators workshop. Dr. Ajani is Professor of Medicine, Department of Gastrointestinal Oncology, M. D. Anderson Cancer Center in Houston, and also served as program chairman for the workshop. The workshop was sponsored by the University of Texas M. D. Anderson Cancer Center, and supported by an unrestricted educational grant from Pharmacia Oncology.
Dr. Ajani summarized data from a recent trial of irinotecan(Drug information on irinotecan) (Camptosar) combined with cisplatin(Drug information on cisplatin) in 38 patients with untreated gastric/gastroesophageal junction cancer. The study did not include patients with esophageal cancer. Thirty-six patients were evaluable at the time of this report.
Irinotecan Plus Cisplatin
Irinotecan was given at 65 mg/m² IV over 90 minutes. Cisplatin was given at 30 mg/m² IVPB over 60 minutes. Both agents were given 1 day a week for 4 weeks, followed by a 2-week recovery period.
Dr. Ajani reported that the median number of cycles given was 2.5, that 15% of cycles were delayed, and that 7% were cancelled. Twenty-two percent of the time, when the patient was scheduled for therapy, it could not be given, he said.
There were 4 (11%) complete responses (CRs) and 17 (47%) partial responses (PRs) for an overall response rate of 58%. The most common grade 3 or 4 toxicities were diarrhea, neutropenia, fatigue, and nausea. A modified dosage schedulesuch as treatment 1 day a week for 2 weeks, then recovery for 1 (day 1, day 8, q 3 weeks)will be tried in an attempt to reduce those problems.
Combined with Radiation
Dr. Ajani said that irinotecan is also being studied in a dose escalation phase I trial in combination with radiation therapy for treating unresectable upper gastrointestinal tract cancers. Radiation therapy is given as 45 Gy for gastric cancer and 50.4 Gy for cancers located in the gastroesophageal junction or above. Irinotecan doses begin at 30 mg/m²/week x 5 doses and increase in increments of 10 mg/m²/week in the subsequent dose level. Among the 25 patients so far enrolled, 6 patients have been treated at the 80 mg/m² dose, Dr. Ajani said, adding that dose escalation will stop there due to toxicity. There have been 4 CRs, 1 PR, and 1 minor response. The recommended phase II dose is not yet established.