Phase-II clinical trial of 4′-epi-doxorubicin in metastatic solid tumors

Abstract

4'-Epi-doxorubicin, one of the analogs of doxorubicin, was shown in experimental animal tumor models to have a wide spectrum of antitumor activity. In comparison, its toxic side effects were less prominent than those of doxorubicin. Results of the first phase-I and II clinical trials in human tumors have confirmed experimental data. The aim of our study was to carry out a broad phase-II clinical trial mainly in various types of primarily chemoresistant solid tumors to obtain further information on the antitumor activity spectrum and toxicity of 4'-epi-doxorubicin. Ninety-two patients, 55 males and 37 females aged from 32 to 75 with an average age of 51 years, were available for the study. Karnofsky performance status was not less than 50. Previous chemotherapy was recorded in 33 patients. The drug was administered at doses of 40 mg/m2 i.v. daily for 2 days in the first 25 patients and, in all other patients, the dosage was increased to 50 mg/m2 i.v. daily for 2 days (100 mg/m2/cycle). The overall response was registered in 18 (seven complete, 11 partial remissions) out of 92 patients (20%). Regarding tumor types, the response was observed in 2/15 lung, 4/15 stomach, 3/14 colorectal, and 5/13 breast cancers. No response was observed in 11 patients with melanoma and five with hypernephroma. Toxicity was mild (myelosuppression, gastrointestinal toxicity, cardiotoxicity) and tolerable for the patients. On the basis of these results, we could conclude that 4'-epi-doxorubicin is an active antitumorigenic agent in breast cancer and in stomach, rectal, and small-cell lung tumors. These results justify further clinical investigation of this compound especially in combination chemotherapy treatment.

Current Status of Epirubicin (Farmorubicin) in the Treatment of Solid Tumours

“…Epirubicin has been studied in phase I1 trials as single agent (199)(200)(201). The doses used have been between 75-100mg/m2 every 3 weeks.…”

Controlled Phase III Clinical Study of 4-Epi-Doxorubicin + 5-Fluorouracil versus 5-Fluorouracil Alone in Metastatic Gastric and Rectosigmoid Cancer

“…These data suggest that 4-epi-DX could be an active agent, but only in rectal and sigmoid cancer. Our personal observation sup ported this statement [12].…”

Phase II trial of 4′-epi-doxorubicin in metastatic colorectal carcinoma

“…4'-Epi-DX has been tested as a single drug mostly in previously treated patients with response rates ranging from 0-25% (5,6). In some studies activity was reported as confined to rectosigmoid carcinoma (7)(8)(9), and recent reviews of the literature also showed a more pronounced activity in rectosigmoid carcinoma than in colon carcinoma (4,10). Only Falkson et al (6) have reported a significant response rate in colon carcinoma (7 out of 26 patients).…”