Arthur Haut

Combination chemotherapy for multiple myeloma

Response rate, remission duration, and survival time were compared in 236 patients with multiple myeloma receiving a melphalan‐prednisone‐procarbazine combination and in 156 patients receiving only melphalan‐prednisone. Response was confirmed when myeloma protein production had been reduced to less than 25% of the pretreatment value. Of the evaluable trials, 59% of patients responded to the procarbazine combination, and 48% to melphalan and prednisone. In both treatment groups, the survival time of all patients (22 months) and the remission duration of responding patients (21 months) were similar. Maximum degrees of myeloma protein reduction were associated with longer remissions and survival. Previously reported resistance to treatment of patients with only lambda Bence Jones protein was not apparent with these superior treatment regimens. Results support the value of combination chemotherapy with melphalan‐prednisone‐procarbazine for remission induction in patients with multiple myeloma.

Alternating Combination Chemotherapy and Levamisole Improves Survival in Multiple Myeloma A Southwest Oncology Group Study

Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.

Superiority of adriamycin‐containing combination chemotherapy in the treatment of diffuse lymphoma. A southwest oncology group study

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non‐Hodgkins lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low‐dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low‐dose bleomycin (COP‐Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP‐Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP‐Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p < 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP‐Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma. Cancer 43:417–425, 1979.

Combination therapy for multiple myeloma

The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3‐week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy‐one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine‐prednisone or a combination of melphalan‐cyclophosphamide‐carmustine (BCNU)‐prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor mass maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated. Cancer 40:2765‐2771, 1977.

Phase II evaluation of bleomycin. A Southwest Oncology Group study

Bleomycin given intravenously (i.v.) or intramuscularly (i.m.) in twice‐weekly doses of 10 mg/m2 was evaluated for efficacy and toxicity in 382 patients. Responses were observed in 11/27 Hodgkins diseases, 10/30 lymphomas, 9/22 squamous cell cancers of ectodermal origin, 12/26 germinal cancers, and 3/8 renal adenocarcinomas. The i.m. route is less, likely to cause pulmonary toxicity or hypotension than the i.v. route. Advanced age and total doses exceeding 200 mg were Associated with a higher risk of lung toxicity. All responders had shown at least improvement upon receiving 200 mg; higher total doses should be used only in responding patients.

CCNU (1‐[2‐chloroethyl]‐3‐cyclohexyl‐1‐nitrosourea, NSC‐79037) in the treatment of cancer. Phase II study

CCNU (1‐[2‐chloroethyl]‐3‐cyclohexyl‐1‐nitrosourea, NSC‐79037), was used to treat 141 evaluable patients with a variety of advanced malignancies, 56% of whom had not received prior chemotherapy. Patients with an adequate bone marrow reserve received 130 mg/m2 as the initial dose and those with an impaired reserve received 100 mg/m2. Therapy was repeated every 6 weeks and the dosage modified according to the hematologic toxicity. Responses greater than 50% reduction in tumor size were noted in 26 patients; stable disease or reduction in tumor size of less than 50% was observed in 21 patients. The well‐differentiated adenocarcinomas and squamous cell tumors appeared to be least sensitive to CCNU. Bone marrow depression was the major dose‐limiting factor. Without adequate antiemetic therapy, all patients would have had nausea and vomiting. Hepatocellular toxicity was noted in two patients.

Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: A southwest oncology group study

Between 1974 and 1977, 652 patients with non‐Hodgkins lymphoma without prior chemotherapy were randomized to 1 of 3 combination chemotherapy programs designed to induce complete remission (CR): COP‐bleomycin (180 patients), CHOP‐bleomycin (232 patients) or CHOP plus immunotherapy with Bacillus Calmette Guerin (BCG) (240 patients). With mature follow‐up, the major effect of BCG immunotherapy was observed in patients with large cell lymphomas (diffuse or nodular “histiocytic”) and not in other common lymphoma subtypes. CR rate for 65 patients with large cell lymphoma treated with CHOP‐BCG was 68% compared to 48% in 61 patients treated with CHOP‐bleomycin (P = 0.02) (two‐tailed test) or 44% for 45 patients treated with COP‐bleomycin (P = 0.02). CR duration for both CHOP‐based regimens was similar and superior to that produced by COP‐bleomycin (P = 0.03). Survival of patients with large cell lymphoma treated with CHOP‐BCG was better than that observed with CHOP‐bleomycin (P = 0.02) or COP‐Bleomycin (P = 0.002). Although the explanation for the favorable effect of BCG remains unclear, further clinical trials to evaluate the combination of chemotherapy and other “biologic response modifiers” is warranted for patients with lymphoma.

A phase II study of methyl CCNU in the treatment of solid tumors and lymphomas: A Southwest oncology group study

In March of 1972, the Southwest Oncology Group initiated a Phase II study, No. 7200, utilizing methyl‐CCNU in the treatment of patients with solid tumors and lymphomas. Initially, they received 200 mg/m2 orally as a single dose every 6 weeks. The dose was subsequently reduced in poor‐risk patients to 150 mg/m2. There were 69 responses noted in 675 evaluable patients (10%). The highest response rates were noted in patients with Hodgkins disease (13/31, 35%), malignant gliomas of the brain (8/29, 28%), anaplastic carcinomas of the lung (5/20, 25%), and squamous cell carcinomas of the head and neck (5/29, 17%). Squamous cell tumors appeared to be more responsive than adenocarcinomas (15% vs. 5%, respectively). Hematologic toxicity was cumulative, and was influenced by dose and prior treatment. There appeared to be no cross‐resistance in patients previously treated with alkylating agents. Methyl‐CCNU is an active antineoplastic agent. Further studies are indicated in order to determine relative effectiveness.

Chemoimmunotherapy for multiple myeloma.

The effect of chemoimmunotherapy consolidation treatment using alternating courses of alkylating agents and BCG was studied in 105 responding patients with multiple myeloma. The survival time of these patients was similar to that of responding patients treated on previous maintenance programs, indicating no apparent value from BCG for myeloma. The duration of unmaintained remission was longest in those with low numbers of residual plasma cells, and relapse usually developed within one year in patients with persistent serum myeloma peaks. Disease recontrol was achieved in 50% of relapsing patients whose median survival from retreatment was 20 months. Patient follow‐up without chemotherapy until relapse was justified mainly for those responding patients with disappearance of myeloma proteins.

Pyridoxine-Responsive Anemia

HYPOCHROMIC, microcytic anemia combined with normal or elevated serum iron is a syndrome characteristically found in patients harboring the thalassemia gene. This syndrome is also encountered in so...HYPOCHROMIC, microcytic anemia combined with normal or elevated serum iron is a syndrome characteristically found in patients harboring the thalassemia gene. This syndrome is also encountered in so...