Robert E. Slayton

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.

Comparative activity and toxicity of cis-diamminedichloroplatinum (DDP) and a combination of doxorubicin, cyclophosphamide, and DDP in disseminated transitional cell carcinomas of the urinary tract.

From October 1978 to October 1981, 135 patients with disseminated transitional cell carcinomas of the urinary tract, with either measurable or evaluable disease, were randomized to receive either cis-diamminedichloroplatinum (DDP) or cyclophosphamide (CTX), Adriamycin (ADR) (Adria Laboratories, Columbus, Ohio), and DDP (CAD). DDP was given at a dose of 60 mg/m2, CTX at 400 mg/m2, and ADR at 40 mg/m2 intravenously every three weeks. Patients over the age of 65 and those with prior radiation received 75% of the dose initially. The dose was escalated if only mild toxicity developed. Of the patients on the CAD arm, 34% developed grade 3 or 4 hematologic toxicity, as compared to 3% in patients on the DDP therapy. Of the 93 patients with measurable disease, 48 received DDP. Seventeen percent had a partial or complete remission, as compared to 33% of the 45 patients on the CAD arm (P = .09). The crude median survival of patients on DDP was 6.0 months as compared to 7.3 months in patients receiving CAD (P = .17). We conclude that the CAD combination is more toxic than DDP with, at best, very marginal benefit in survival.

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.

Neuroendocrine carcinoma of the cervix: Implications for staging and therapy

Abstract Ultrastructural examination of four cases of small cell carcinoma of the cervix demonstrated neuroendocrine granules. In each of these cases, distant metastases became evident within 3 months of the initial diagnosis. The sites of metastases included liver, brain, bone marrow, and supraclavicular lymph nodes. Because of light microscopic, ultrastructural, and clinical similarities to pulmonary neuroendocrine carcinoma, three of these patients received combination chemotherapy effective in neuroendocrine tumors arising in the lung. One patient experienced remission of bulky pelvic tumor and supraclavicular metastases which lasted 11 months.

Gallium-67 imaging in the management of Hodgkin's disease and other malignant lymphomas

Gallium-67 imaging is useful in the management of patients with malignant lymphoma, despite its obvious limitations. Data currently in the literature regarding the detectability of sites of lymphoma by 67Ga imaging should be regarded as representing the minimum that can be expected from the method, since all reported series are based on outmoded imaging techniques. The detectability of disease sites appears to vary with tumor histology and anatomic location. Gallium-67 imaging is most useful in following patients after treatment. However, it may justifiably play an important role in the initial staging of lymphoma if the prior probability of disease in the abdomen is low. Lymphoma in abdominal lymph node sites is at least as detectable by 67Ga imaging as by lymphangiography.

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.

Retiform Differentiation in Ovarian Sertoli-Leydig Cell Tumors A Clinicopathologic Study of Six Cases From a Gynecologic Oncology Group Study

This report analyzes six ovarian Sertoli‐Leydig cell tumors that showed retiform differentiation. The patients were young (6–29 years; average age, 17). The tumors were all limited to one ovary, and the patients have remained disease‐free, with one exception, a patient who died of recurrent neoplasm 3.5 years after operation. On microscopic examination, the retiform areas were predominant in three cases and focal in the other three. The retiform areas consisted of an irregular anastomosing network of spaces lined by cuboidal cells, often with papillary formations and sometimes with tubules compressed to form slit‐like spaces. In three cases the retiform areas appeared mature, and in three they were less differentiated. All tumors also had areas of typical Sertoli‐Leydig cell tumor of either poor or intermediate differentiation. In the patient with metastatic disease, the metastases had a pure sarcomatoid pattern without any retiform areas.

A phase II clinical trial of diaziquone (AZQ) in the treatment of patients with recurrent leiomyosarcoma of the uterus

SummaryBased upon the activity observed in this trial, there does not appear to be a significant role for AZQ as a salvage agent for leiomyosarcoma of the uterus at the dose and schedule tested.

Primary retroperitoneal pure choriocarcinoma. Two long‐term complete responders from a rare fatal disease

Extragonadal germ cell tumors may have a worse prognosis than germ cell tumors of gonadal origin, even when tumor bulk and extent of dissemination are equal. Primary retroperitoneal pure choriocarcinoma is one of the least common subgroups of the extragonadal germ cell tumors and has previously appeared to have the worst prognosis. Two new case reports on the treatment and follow‐up of two patients with primary retroperitoneal pure choriocarcinoma are discussed. Both patients are diseasefree at 24 and 81 months, respectively. After aggressive primary multiagent drug therapy for primary retroperitoneal pure choriocarcinoma, a favorable prognosis may be anticipated.

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.