mitolactol and Adenocarcinoma

To evaluate a combination of thioguanine, procarbazine, dibromodulcitol, CCNU (CCNU), fluorouracil, and hydroxyurea (TPDC-FuHu), designed to improve the efficacy of CCNU, in the treatment of recurrent metastatic brain tumors.. One hundred fifteen patients with progressive or recurrent metastatic brain tumors that failed to respond to surgery and/or radiation therapy were enrolled onto a multicenter prospective study between 1989 and 1995. Patients received TPDC-FuHu in a repeated cycle every 6 weeks until recurrence or until they completed six courses.. Ninety-seven patients were assessable at the end of the study. Forty-eight had lung cancer (39 non-small-cell [NSCLC] and nine small-cell [SCLC]), 28 had breast cancer, nine had melanoma, and 12 had adenocarcinoma of different origins (three colon, two kidney, one bladder, one stomach, and five of unknown origin). The response and stable disease (SD) rate (overall response rate) was 52%, 66%, 60%, and 22% in patients with NSCLC, SCLC, breast cancer, and melanoma, respectively. Median time to progression (MTP) was 12, 26, 12, and 6 weeks, respectively, for the four groups. Side effects were mild to moderate in the majority of patients. Severe myelosuppression (grade 4) occurred in only 11% of the patients.. TPDC-FuHu chemotherapy is an active treatment against recurrent brain metastases from breast cancer and SCLC, and to a lesser extent from NSCLC. This regimen is well tolerated and has acceptable toxicity.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Disease Progression; Female; Fluorouracil; Humans; Hydroxyurea; Lomustine; Lung Neoplasms; Male; Middle Aged; Mitolactol; Procarbazine; Prospective Studies; Thioguanine

Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with mitolactol, doxorubicin, vincristine (DAV), tamoxifen, and fluoxymesterone (DAVTH). Nine patients were canceled, and 114 were ineligible (half because of concomitant diseases). Among the 501 eligible patients, the overall response rate was 54% (14% complete response and 5% not assessable). The median time to treatment failure (TTF) was 9.0 months, and the median survival was 20.9 months. Multivariate models were fit on a randomly chosen half of the eligible cases and then verified on the other half. About half of the variables that were significant in the models remained significant in the verification data set. In the verification data set the variables that remained significantly associated with lower probability of response were three or more organ sites of disease and lack of nodal metastases; the variables associated with a significantly shorter TTF were liver metastases, estrogen receptor (ER)-negativity, and prior adjuvant therapy. The variables associated with significantly shorter survival were liver metastases, ER negativity, three or more organ sites of disease, and prior adjuvant chemotherapy. None of the variables in the data set had a significant influence on toxicity. The 125 patients aged over 65 years did not have worse toxicity or worse prognosis than younger patients. Ineligible patients had significantly less response but virtually identical TTF curves, survival curves, and toxicities. Therefore, patient discriminants are of paramount importance in predicting the outcome of treatment. Many of the current criteria for eligibility for entry on study may not be justified.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Middle Aged; Mitolactol; Multivariate Analysis; Prognosis; Proportional Hazards Models; Survival Analysis; Tamoxifen; Treatment Outcome; Vincristine

A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients entered on the study were stratified into groups according to stage of disease and cell type. The results showsed Hexamethylmelamine to be more effective in patients with squamous cell carcinoma and slightly superior to Dibromodulcitol in patients with anaplastic/undifferentiated cell carcinoma, whereas Dibromodulcitol proved to be more effective in patients with adenocarcinoma.

Topics: Adenocarcinoma; Altretamine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Evaluation; Humans; Leukopenia; Lung Neoplasms; Middle Aged; Mitolactol; Nausea; Thrombocytopenia; Triazines; Vomiting

Two Adriamycin (doxorubicin)-based chemotherapy regimens were investigated in patients with carcinoma of the breast who had failed prior systemic therapy. The two chemotherapy programs, dibromodulcitol, Adriamycin, vincristine, and Halotestin (fluoxymesterone) (DAVH), and thiotepa, Adriamycin, vinblastine, and Halotestin (TAVH), were chosen for comparison on the basis of reported response rates of 40% to 50% with remission durations of 11 months in patients refractory to other cytotoxic chemotherapy. Cycles of DAVH were repeated every 4 weeks. Cycles of TAVH were repeated every 3 weeks. Of 184 patients evaluable for response, 32% of patients treated with DAVH and 38% of patients treated with TAVH had a complete response (CR) or partial response (PR). An additional 5% of patients had nonmeasurable improvement in osseous disease for an overall rate of response (CR + PR + improvement) of 40%. Patients who had previously received cytotoxic chemotherapy for metastatic disease or had early failure after adjuvant therapy had a lower response rate to DAVH, but not to TAVH than those who did not fail prior chemotherapy. Duration of response and survival were similar with the two treatments. There were seven treatment-related deaths, five among patients receiving DAVH and two among patients receiving TAVH. Patients receiving DAVH had significantly more thrombocytopenia and neurologic toxicity than those receiving TAVH. These treatments appear to be reasonable second-line regimens and are good candidates to be used in initial therapy of metastatic disease or adjuvant therapy studies that explore the use of alternating non-cross-resistant combinations with cyclophosphamide, methotrexate, and 5-fluorouracil.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Fluoxymesterone; Humans; Leukopenia; Middle Aged; Mitolactol; Neoplasm Recurrence, Local; Nervous System Diseases; Thiotepa; Thrombocytopenia; Vinblastine; Vincristine

Topics: Adenocarcinoma; Adult; Aged; Drug Evaluation; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Mitolactol

Topics: Adenocarcinoma; Colonic Neoplasms; Drug Evaluation; Female; Humans; Leukopenia; Male; Middle Aged; Mitolactol; Rectal Neoplasms