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Conrad Notes
a timely medical meeting newsletter
Y. Shimizu, MD, PhD, Cancer Institute Hospital, Tokyo, Japan, found combined use of CPT-11 (irinitecan) and mitomycin-C (MM-C) promising as therapy for Stage III OCCA. Intravenous infusion of both agents to 28 platinum-resistant OCCA patients led to an overall response rate (RR) of 50%. Moderate diarrhea developed in three patients and moderate or severe neutropenia in 18 of the 95 cycles. (Please see the package insert on irinotecan).
Background on CPT-11 and MM-C CPT-11 specifically inhibits topoisomerase I, resulting in irreversible DNA damage and cell death. Irinotecan is approved for treating colorectal cancer resistant to 5-fluorouracil (5-FU).

MM-C suppresses the synthesis of DNA and RNA. Combined with other approved drugs, MM-C is effective in treating disseminated carcinoma of the stomach and pancreas.

Demography of study patients Twenty-eight females with confirmed stage 3 or 4 OCCA qualified for the study. OCCA had progressed during platinum-based chemotherapy or relapsed within 6 months of such treatment. Eight of the platinum-resistant OCCA patients failed to respond to previous use of CPT-11 alone.
Intravenous dosing with CPT-11 and MM-C All patients received both drugs intravenously on Day 1, 15, and 29 of each monthly dosing cycle. CPT-11 infusion took place over a 4-hour period at a dose of 130 mg/msq. The dose of MM-C was 7 mg/msq. Repeat treatment with both agents occurred at 3 to 4 week intervals totalling 95 cycles for the 28 patients.
Toxicity of combined treatment Moderate to severe neutropenia developed in 18 of the 95 treatment cycles. These patients were managed with granulocyte colony stimulating factor (GCSF). The other toxic signs, alopecia and severe diarrhea, were acceptable to Shimizu.
Survival and response rates Preliminary data on 28 patients show a median survival of >21 months for 14 responders and 7 months for 14 nonresponders (p<0.01). Shimuzu categorized patients showing a complete (CR) or partial response (PR) according to OCCA tumor diameter:

Diam.(cm) No. Pts. Complete Partial
< 2 6 3 2
2-5 11 2 5
> 5 11 0 2

The overall response rate was 50%.

Investigator conclusions Shimizu reported CPT-11 plus MM-C as the first regimen to significantly improve survival in platinum-resistant OCCA patients. The acceptable toxicity of this combination supports undertaking a study in previously untreated OCCA patients.

For professional correspondence, please contact Dr. Shimizu by E-mail at: yshimizu@jfcr.or.jp

Eugene A. Conrad

Presented at The European Cancer Conference (ECCO 9), September 14-18, 1997
Copyright © 1997 Conrad Group, Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / November 1997
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