HOUSTON"Cisplatin (Platinol) has served us well, but we
need to move on and study combinations with less toxic 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
Dr. Ajani summarized data from a recent trial of irinotecan
(Camptosar) combined with 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.