John N. Bickers

Adriamycin combinations in advanced breast cancer. A Southwest Oncology Group Study.

The Southwest Oncology Group tested three combinations of drugs with Adriamycin to identify a best regimen for treatment of advanced breast cancer. Adriamycin, cyclophosphamide, and 5‐fluorouracil (5FU)(FAC); Adriamycin and cyclosphosphamide (AC); and Adriamycin followed by cyclophosphamide, vincristine, methotrexate, 5FU, and prednisone (A + COMFP) were used in a prospective randomized study of 497 patients with previously untreated metastatic breast cancer.

Genetic studies in multiple myeloma 1. Association with HLA-Cw5

Human leukocyte antigens (HLA) were identified in 22 black Americans with multiple myeloma. No significant association was observed between antigens at either the A or the B locus. At the C locus, in contrast, HLA‐Cw5 was more prevalent in the patient group, four of 22 having it, compared with the control group, in which two of 138 individuals possessed it. All four patients with HLA‐Cw5 were males. Those results suggest that genetic factors, perhaps in conjunction with an environmental change, may be responsible for the recent increase in incidence in myeloma in black Americans, especially in males.

Phase II trial of didemnin-B in advanced epithelial ovarian cancer

SummaryA Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicities were nausea and vomiting and anemia. On the basis of this trial, Didemnin-B is not felt to have significant effect with epithelial ovarian cancer.

A Comparison of Metoclopramide Vs. Droperidol/Phenobarbital for Emesis Induced by Chemotherapy

Chemotherapy-induced nausea and vomiting cause morbidity and poor compliance among patients receiving intensive cancer chemotherapy. High-dose antiemetic regimens, while effective, add significantly to the cost of treatment. This study compares the efficacy and cost of high-dose metoclopramide with a combination of phenobarbital and droperidol. All patients treated were naive to prior chemotherapy, and all patients received treatment regimens containing cisplatinum. Both antiemetic regimens proved equally efficacious in suppressing emesis, but the phenobarbital/droperidol combination achieved a 100-fold decrease in cost.

Progressive hypersplenism after portacaval anastomosis

SummaryThree patients are presented who developed severe manifestations of hypersplenism after portacaval anastomosis for cirrhosis with esophageal varices. All 3 patients ultimately required splenectomy, after which they were much improved, though a mild anemia persisted.The possible mechanisms for the production of post-shunt hypersplenism and the clinical implications are discussed.

Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial.

SummaryInterferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I–II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0×106 IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table.Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.

RADIOISOTOPES IN THE DIAGNOSIS OF HEMATOLOGIC MANIFESTATIONS OF GASTROINTESTINAL DISEASE

D ISORO~RS of the gastrointestinal tract are accompanied by many and varied hematologic abnormali t ies; the manifestat ions of the latter f requently overshadow those of the pr imary disease. These secondary blood changes serve to indicate the nature, as well as the presence, of digestive tract disease. An unders tanding and appreciat ion of this intimate relat ionship is prerequisi te to an intelligent approach to diagnosis and management of diseases involving either system. T h e following material deals with some of the major hematologic abnormali t ies which are frequently the consequence of digestive-tract disease. Specifically, the role of radioisotopes in the diagnosis of these disorders will be considered. T h e technics discussed are those which are generally applicable in the average clinical radioisotope laboratory.