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Biomedical subjects

A Haut

Publications and source records attributed to A Haut.

17 recordsLinked to original sources

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-Hodgkin's 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 less than 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.

Antineoplastic Agents

Phase II evaluation of hexamethylmelamine in advanced breast cancer: a Southwest Oncology Group study.

Ninety-eight patients with metastatic breast cancer, heavily pretreated with other agents, were entered in a phase II trial of hexamethylmelamine (HEX). Patients were randomized to receive HEX alone or combined with prophylactic pyridoxine. There was a 2% response rate in 89 partially or fully evaluable patients. Seven percent of these patients developed neurologic toxicity which occurred in the HEX-alone group only.

Aged

Chemotherapy of acute leukemia: a comparison of vincristine, cytarabine, and prednisone alone and in combination with cyclophosphamide or daunorubicin.

Adults (274) with acute leukemia (AML) were randomly assigned to one of three treatment regimens: vincristine, prednisone, cytarabine--(1) 100 mg/sq m/day with cyclophosphamide (COAP); (2) 100 mg/sq m/day with daunorubicin (DOAP); and 200 mg/sq m/day (OAP). Cytarabine was infused continuously for five days. Patients entering complete remission randomly received maintenance treatment with COAP or OAP. For 197 previously untreated AML patients given COAP, DOAP, or OAP, remission rates were 37%, 35%, and 43%, respectively; median lengths, 40, 45, and 90 weeks; median survival, 7, 11, and 8 weeks. No statistically significant difference was found among treatments. Therefore, adding cyclophosphamide or daunorubicin, or using the COAP regimen with continuously infused cytarabine, produced no significant improvement over previously reported regimens. There was no significant difference in remission lengths in previously untreated AML patients maintained on OAP (median 81 weeks) or COAP (median 65 weeks).

Acute Disease

Piperazinedione in patients with advanced malignant melanoma: a Southwest Oncology Group study.

Piperazinedione was administered in doses of 9 or 12 mg/m2 by iv infusion every 3 weeks in 28 patients with previously treated malignant melanoma. Of the 25 evaluable patients, 72% had drug-induced toxicity: 40% had leukopenia, 56% had thrombocytopenia, 40% had anemia, and 16% had nausea and vomiting. None of these patients had partial remission, two had stable disease, and the remaining 23 had definite progression of their disease in spite of adequate trial with this agent.

Adult

Unmaintained remissions in multiple myeloma.

Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

Cell Transformation, Neoplastic

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 was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.

Antineoplastic Agents

Pulmonary fibrosis after prolonged therapy with 1,3-bis (2-chloroethyl)-1-nitrosourea.

A 43-year-old man with metastatic malignant melanoma was treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in combination with imidazole carboxamide and hydroxyurea. He achieved complete remission. After 22 months of chemotherapy, the patient developed bilateral pulmonary infiltrates. Open lung biopsy showed sclerosing alveolitis. Long-term therapy with BCNU may cause pulmonary fibrosis, as has been seen with other cytotoxic drugs.

Adult

Phase II trial of piperazinedione in Hodgkin's disease, non-Hodgkin's lymphoma, and multiple myeloma: a Southwest Oncology Group study.

Piperazinedione given iv once every 3-4 weeks at a starting dose of 9-12 mg/m2 (4.5-12 mg/m2 for patients with myeloma) was evaluated in a Southwest Oncology Group phase II study for patients with far-advanced refractory lymphoma or multiple myeloma. Among 36 patients fully evaluable for tumor response (adequate trial), partial responses were observed in five (71%) of seven patients with Hodgkin's disease, in three (19%) of 16 patients with non-Hodgkin's lymphoma, and in none of 13 patients with multiple myeloma. Response was observed by the time of the second (five patients) or third (three patients) course. The median duration of response was 3.7 months (range, 1-17+ months). The dose-limiting toxic effects were hematologic, with 18 (50%) of 36 patients evaluable for toxicity experiencing severe leukopenia (wbc count less than 2000/mm3) and 22 (61%) experiencing severe thrombocytopenia (platelet count less than 50,000/mm3). Twenty patients had a decrease from their pretreatment hemoglobin level of greater than or equal to 2 g/100 ml. Hematologic toxic effects were often unpredictable and in several patients quite prolonged. This study indicates that piperazinedione had definite antitumor activity in patients with Hodgkin's disease and further trials in this disease using the drug at a reduced dose in combination with other effective drugs appear warranted.

Antibiotics, Antineoplastic

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 Hodgkin's 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 casue 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.

Adenocarcinoma

Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma.

Combination chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone) and HOP (Adrimycin, vincristine, and prednisone, was used as treatment for patients with pathologically staged, advanced non-Hodgkin's lymphoma. Among 204 evaluable patients treated on CHOP there were 71% complete remissions with 92% overall responses. Among the 216 evaluable patients on HOP there were 61% complete remissions and 88% responses. Complete remission rates among patients with histiocytic lymphoma were comparable to those of patients with lymphocytic disease. Patients with nodular lymphoma had higher rates of complete remission than their counterparts with diffuse lymphoma. This was noted with both CHOP (78% vs. 67%) and HOP (67% vs. 60%) induction therapy. Rapid responses were common, as more than 14% of complete remissions and 66% of overall responses were achieved with the first course of treatment. Patients in complete remission have been maintained with either cyclophosphamide, vincristine, and prednisone (COP) or arabinosyl cytosine, vincristine, and prednisone (OAP). After 1 year, 86% of patients on COP and 80% on OAP are projected to be free of disease.

Cyclophosphamide

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 Hodgkin's 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.

Adenocarcinoma

Prognostic factors in multiple myeloma.

The effect of certain disease parameters on remission and survial time was evaluated in 482 patients with multiple myeloma treated with intermittent courses of melphalan-prednisone combinations. Increasing degrees of anemia, hypercalcemia, azotemia, and high serum myeloma protein levels were associated with progressive lifespan shortening. The short survival of patients with anemia and hypercalcemia was associated with short remissions in responding patients with these abnormalities. The extent of tumor mass was defined from specific laboratory parameters reported by Durie to be associated with large numbers of plasma cells. More advanced stages of myeloma were associated with higher frequencies and degrees of normal immunoglobulin depression. The response rate was not affected by the tumor mass grade, but increasing tumor mass was associated with a shorter lifespan. Greater degrees of tumor reduction were associated with longer remission and survival times. Patients in whom a marked tumor reduction was rapid had shorter survival and remission times than patients who responded more slowly.

Aged

CCNU and bleomycin in the treatment of cancer: a Southwest Oncology Group Study.

CCNU and Bleomycin, alone or in combination, were used to treat 397 evaluable cases of advanced cancer. Responses defined as 50% or greater reduction in all tumor masses occurred in 13/35 lymphomas, 8/50 brain cancers, and 28/312 other solid tumors. Hematologic toxicity of a life-threatening degree occurred in 33/298 patients evaluable for CCNU toxicity; in an additional 50 it was considered severe. Pulmonary toxicity was severe in 4 patients. Drug-associated deaths (4) included one each due to leukopenia and thrombocytopenia after CCNU; one due to pulmonary toxicity after Bleomycin; and one due to shock after the 20th dose of Bleomycin. There was no suggestion of synergism or additive activity with the two drugs.

Adenocarcinoma