pirarubicin and Melanoma

Eighty patients with measurable metastatic colon or renal cancer, melanoma, or sarcoma entered these Phase II studies. A dose of 25 mg/m2/day of Pirarubicin (THP) for 3 consecutive days every 4 weeks for the first patients, and then 20 mg/m2/day for 3 days every 3 weeks was given by i.v. push. These patients received 225 cycles for a median cumulative dose of 165 mg/m2 (range: 55-630). The mean number of cycles given was 2.8 (range: 1-8). Only 3 partial responses and 18 stable disease (22%) were observed. Hematologic toxicity was the main problem; it was responsible for one death and a 19% and 44% incidence of grade 3 and 4 WHO neutropenia, respectively. Alopecia was rare (4%). Chemotherapy was discontinued in three cases because of suspicion of cardiac toxicity, but only one patient had a significant drop in left ventricular ejection fraction at a cumulative THP dosage of 120 mg/m2. A lack of efficacy in renal and colon cancer and melanoma was presupposed and confirmed by these trials. Due to pretreatment with anthracycline in most patients, definite evaluation of THP in soft tissue sarcoma could not be given.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Humans; Kidney Neoplasms; Melanoma; Middle Aged; Sarcoma; Soft Tissue Neoplasms

The survival rate of human melanoma cells after X-ray irradiation, treatment with adriamycin derivatives and combined treatment with X-rays and adriamycin derivatives was measured by means of the colony formation test. After X-ray irradiation the melanoma cells showed a high resistance for cell survival. In all tests the Be11-cells were more resistant than MeWo-cells. On combined exposure especially with higher doses of adriamycin derivatives, both cell lines showed the interesting effect, that with increasing concentration the survival rate decreased whereas the D(o) increased. Aclacinomycin-A (ACM-A) and Pirarubicin reduced recovery processes after X-ray irradiation. Therefore Be11-cells showed a four times higher DMF (dosis modifying factor) after ACM-A-treatment than MeWo-cells. Low ACM-A-concentrations combined with low X-ray doses showed on both cell lines supraadditive effects. The effect of pirarubicin was in most of the tests only additive. Compared with ACM-A, pirarubicin was less cytotoxic, showed a larger therapeutic range, caused a smaller D(o) and Dq and had a supraadditive effect in low concentrations on both cell lines. For clinical combined therapy with patients ACM-A is probably better suited than pirarubicin.

Topics: Aclarubicin; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Doxorubicin; Humans; Melanoma

Chemotherapy with 4'-O-tetrahydropyranyladriamycin (THP-ADM), a new derivative of Adriamycin, was equally or more effective against several experimental mouse tumors than it was with Adriamycin (ADM). When mice with P388 leukemia were given i.p. injections of THP-ADM or ADM daily for 9 consecutive days, the maximum increases in life span (ILSs) of the mice were 190 and 175%, respectively. Eight of 24 mice treated with THP-ADM were free of tumor, while one of 24 mice treated with ADM was free of tumor. A single i.p. injection of either drug was also effective; maximum ILS was 170% for mice treated with THP-ADM and 240% for those treated with ADM. Nine of 12 mice were found to be free of tumor. THP-ADM was equally or slightly more effective against P388 leukemia than was ADM when either drug was given i.v. The maximum ILS was 106% with THP-ADM and 77% with ADM when the drug was given for 9 consecutive days. Single i.v. injections of THP-ADM or ADM were almost equally (ILS, 100%) effective. Chemotherapy with THP-ADM was also very effective against L1210 leukemia. THP-ADM administered i.p. five times, every other day starting from Day 1, was more effective than ADM was against Lewis lung carcinoma, B16 melanoma, and colon adenocarcinoma 38 inoculated s.c. In the study with Lewis lung carcinoma, metastasis to the lungs was well suppressed by THP-ADM. ADM was more effective than was THP-ADM against colon adenocarcinoma 26. Because THP-ADM was more cytotoxic than or almost equally as cytotoxic as ADM against the established cell lines from the above mouse tumors, we suggest that THP-ADM is more efficiently transported into cultured cells.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cell Line; Colonic Neoplasms; Doxorubicin; Leukemia P388; Lung Neoplasms; Melanoma; Mice; Mice, Inbred Strains; Neoplasms, Experimental