ABSTRACT
Oral 6-thioguanine (6-TG) is an S-phase antimetabolite with significant activity against acute leukemia. Preliminary reports of activity of iv 6-TG indicated significant activity against advanced colorectal cancer. We conducted a phase II study of iv 6-TG in 29 patients with advanced measurable colorectal cancer. Only one transient partial response occurred. Toxic effects included mild myelosuppression, nausea, vomiting, and minor ECG changes. We discourage further use of iv 6-TG in the dose and schedule we used to treat advanced colorectal cancer.
Subject(s)
Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Thioguanine/therapeutic use , Aged , Drug Evaluation , Female , Heart/drug effects , Heart/physiopathology , Humans , Injections, Intravenous , Middle Aged , Myeloproliferative Disorders/chemically induced , Nausea/chemically induced , Thioguanine/adverse effects , Vomiting/chemically inducedSubject(s)
Adenocarcinoma/drug therapy , Aspartic Acid/analogs & derivatives , Colonic Neoplasms/drug therapy , Organophosphorus Compounds/therapeutic use , Phosphonoacetic Acid/therapeutic use , Adult , Aged , Aspartic Acid/adverse effects , Aspartic Acid/therapeutic use , Colonic Neoplasms/pathology , Drug Administration Schedule , Drug Eruptions/etiology , Drug Evaluation , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Phosphonoacetic Acid/adverse effects , Phosphonoacetic Acid/analogs & derivativesSubject(s)
Colonic Neoplasms/drug therapy , Cyclic N-Oxides/therapeutic use , Pyrrolizidine Alkaloids/therapeutic use , Clinical Trials as Topic , Colonic Neoplasms/pathology , Cyclic N-Oxides/adverse effects , Drug Administration Schedule , Drug Evaluation , Humans , Neutropenia/chemically induced , Pyrrolizidine Alkaloids/adverse effects , Thrombocytopenia/chemically inducedABSTRACT
The value of immunotherapy as an adjuvant to chemotherapy for advanced breast cancer is an unsettled question. To clarify this issue, 71 women with measurable or evaluable metastatic breast cancer were randomized to receive cyclophosphamide, 5-fluorouracil, and prednisone (CFP) with or without methanol-extracted residue of Bacillus Calmette-Guerin (MER). The total regression rates were 52% (CFP) and 39% (CFP + MER), including complete regression rates of 13% (CFP) and 65% (CFP + MER). The median duration of regressions for CFP-treated patients was 257-261 days and for CFP + MER-treated patients was 385 days. The median time to progression was 248-261 days in the CFP group and 159 days in the CFP-MER group. Projected median survival for both treatment groups is 20 months. Immunotherapy (MER) as used in this study does not appear to augment regression rates or vurvival for patients with advanced breast cancer receiving CFP.
Subject(s)
Antineoplastic Agents/administration & dosage , BCG Vaccine/therapeutic use , Breast Neoplasms/therapy , Antineoplastic Agents/adverse effects , Bone Marrow/drug effects , Clinical Trials as Topic , Cyclophosphamide/administration & dosage , Drug Therapy, Combination , Female , Fluorouracil/administration & dosage , Humans , Middle Aged , Prednisone/administration & dosage , Remission, Spontaneous , Time FactorsABSTRACT
Forty-one patients with proven metastatic adenocarcinoma of the lung were randomized into two comparable groups after stratification for performance status and presence of measurable or evaluable disease. Treatment 1 consisted of cis-dichlorodiammineplatinum(II) (P) at a dose of 15 mg/m2/day by iv push on Days 1--5 every 4 weeks. Upon progression or the onset of renal toxic effects, patients were crossed over to cyclophosphamide (C) at a dose of 400 mg/m2, and adriamycin (A) at a dose of 40 mg/m2, both given by iv push on Day 1 every 4 weeks. Treatment 2 (CAP-I) consisted of C-A in the same doses as above plus concurrent P, 40 mg/m2 by IV push on Day 1 every 4 weeks. Eight patients receiving P developed serum creatinine values greater than or equal to 1.5 mg/100 ml versus one patient receiving CAP-I (P = 0.05). Objective regressions occurred in two of 22 patients with P, five of 17 with C-A, and eight of 19 with CAP-I (P = 0.025; CAP-I versus P). There was a significant increase in the median duration of regression in patients responding to C-A following P (267 days) versus patients responding to CAP-I (95 days). The improved rate of response with CAP-I and the prolonged duration of response with C-A following P suggest a potentiating effect between P and C-A whether given simultaneously or sequentially.
