Charles P. Perlia

Prognostic effect of weight loss prior tochemotherapy in cancer patients

The prognostic effect of weight loss prior to chemotherapy was analyzedusing data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkins lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Preliminary clinical experience with cis-diamminedichloroplatinum (II) (NSC 119875, CACP)

Thirty‐one patients with metastatic cancer were treated with cis‐diamminedichloroplatinum (II), CACP, in dosages ranging from 7.5 to 200 mg/m2 BSA per course. Twenty‐two patients received more than one course. Toxicity to the initial course of CACP, up to 90 mg/m2 BSA, was minimal and transient in most patients. At higher dosage levels or following repeat courses, the drug‐related toxicity was more severe. Drug‐related toxicity was more severe in patients with abnormal excretory tracts. The most common and earliest side effects were nausea and vomiting. Hyperuricemia commonly occurred shortly after administration of CACP. A dosage‐dependent, generally transient, nephrotoxicity was noted within the first 10 days after a course of CACP. Moderate leukopenia and thrombocytopenia, as well as a progressive normocytic anemia with marrow erythroid hypoplasia, were observed as late as 3 to 4 weeks after injection of this agent. Audiologic impairment above the frequency range of normal speech was detected by audiometry. Objective tumor regression was seen in five patients, four of whom experienced moderate‐to‐severe toxicity.

Mithramycin treatment of hypercalcemia

An experience with Mithramycin in the treatment of hypercalcemia of malignancy is reported. Mithramycin given by direct, single, intravenous injection of 25 μg/kg was effective in lowering serum calciums within 24 to 48 hours in the majority of patients studied. The duration of this effect has been quite variable, but repeated doses of single injections have proven to be successful in most cases treated. The potential clinical usefulness of this agent in the treatment of hypercalcemia is apparent. It is reasonable to continue such studies on a long‐term basis. Such studies are currently in progress.

Comparison of induction chemotherapies for metastatic breast cancer. An eastern cooperative oncology group trial

Patients with advanced breast carcinoma and no prior chemotherapy were prospectively evaluated to assess the Induction capabilities of cyclophosphamide, methotrexate and 5‐fluorouracil (CMF), Adriamycin and vincristine (AV), and CMF plus prednisone (CMFP). The crossover responsiveness from CMF or CMFP to AV and of AV to CMF were also assessed. A disproportionate randomization led to 166 analyzable cases on AV, 79 on CMF and 86 on CMFP Induction. One hundred and twelve patients were evaluated on crossover. Induction response rates were similar with 56% on AV, 57% on CMF and 63% on CMFP. Crossover response rates ranged from 32% to 41%. CMFP and AV were superior to CMF in terms of response duration (P = 0.05), and CMFP was superior to either in terms of time to treatment failure (P = 0.04), and survival (P = 0.03). Treatment failures occurred in only the on‐study organ sites of disease in 73% of the patients and did not appear to be related to the response achieved. CMF was associated with more thrombocytopenia than either AV or CMFP (P = 0.03). AV was associated with fewer infections than CMFP (P = 0.02), less diarrhea than CMFP (P = 0.04), more emesis than CMF (P = 0.02), and more neurologic toxicity than either CMF or CMFP (P < 0.0001). There was also more emesis with CMF than with CMFP (P = 0.006). CMFP was associated with greater delivery of CMF than was the CMF regimen despite a similar day 1 leukocyte distribution. These results strongly suggest that CMF(P) and AV are clinically noncross‐resistant regimens, that AV and CMF are essentially equivalently active induction regimens, and that CMFP is superior to CMF and AV.

Clinical study with bleomycin

Bleomycin is an antitumor antibiotic produced by Streptomyces verticillus. Seventy‐five patients with various neoplasms were studied using this drug. Fourteen out of 20 patients with epidermoid carcinoma of the head and neck region, 5 out of 14 cases of lymphoma including Hodgkins disease, 3 out of 6 patients with testicular tumors, and one patient with lymphangiosarcoma of the arm showed evidence of objective regression. Common side effects encountered were hyperthermic reactions, gastrointestinal disturbances, hyperkeratosis and vesiculation of fingers, alopecia, and stomatitis. Pulmonary fibrosis is a rare but serious complication. One patient in this series died of this complication. There was no evidence of bone marrow, liver, or renal toxicity. Bleomycin promises to be a useful therapeutic agent and merits further study.

New approach to the treatment of hypercalcemia The effect of short‐term treatment with mithramycin

An intravenous bolus injection of mithramycin (25 μg per kilogram) was given to patients with malignancy‐related hypercalcemia persisting after hydmtion. In most instances a gradual but steady fall in the serum calcium occurred within the next 48 hours, accompanied by a fall in serum inorganic phosphate and 24 hour urinary calcium excretion. Patients with head and neck cancer, cancer of the lung, and multiple myeloma were somewhat less responsive as a group than patients with cancer of the breast or kidney. Aside from transient nausea and vomiting, side effects were minimal. Small doses of mithramycin inhibit bone resorption; dactinomycin and other RNA inhibitors block the action of vitamin D in vitro. The hypocalcemia following administration of these agents may be an expression of their antivitamin D action.

Comparison of intensive versus moderate chemotherapy of lymphocytic lymphomas. A progress report

In an Eastern Cooperative Oncology Group trial, Cytoxan‐prednisone (CP) Induction was compared to BCNU‐prednisone (BP) in 273 patients with lymphocytic lymphoma. Response rates were comparable, with 21% achieving complete response and 40%, partial response. Patients with a nodular pattern responded better. Maintenance phase comparing cyclic intensive therapy (BCVP) with intermittent chlorambucil revealed the superiority of BCVP as demonstrated by improvement of the quality of response and somewhat longer remissions. The value of the Rappaport classification in the evaluation of lymphoma chemotherapy results is discussed. It is suggested that NHL be separated into “favorable” and “unfavorable” groups, based on the presence or absence of nodularity and treatment schedules devised accordingly.

Mithramycin in the treatment of metastatic Ewing's sarcoma.

Five patients with progressive, metastatic Ewings sarcoma were treated with infusions of mithramycin. Two had excellent regressions of their tumors; one patient has no clinical evidence of tumor more than 7 years after mithramycin was given. Patients who are resistant to cyclophosphamide may respond to mithramycin and vice versa. The exact role of mithramycin in patients with Ewings sarcoma is not known. Further experimental trials are indicated with mithramycin alone and in combination both as adjunctive therapy and for the treatment of metastatic disease.

Combination chemotherapy with bleomycin and methotrexate in recurrent and disseminated cervical carcinoma: A preliminary study

Abstract The toxicity and effectiveness of a combination of bleomycin and methotrexate was studied in eight patients with metastatic or recurrent squamous cell carcinoma of the cervix. Three patients had disappearance of measurable disease, two had measurable decrease in volume of tumor, and one had symptomatic improvement without measurable change in lesions. Major toxicity included stomatitis, diarrhea, and hyperpigmentation. Case reports of complete responders are presented.

CRITICAL ANALYSIS OF PALLIATION PRODUCED BY ADRENALECTOMY IN METASTATIC CANCER OF THE FEMALE BREAST

Excerpt INTRODUCTION In the absence of any definitive cure, retardation of tumor growth with prolongation of a comfortable and useful life is a worth while achievement in the treatment of patients ...