John S. Macdonald

5-fluorouracil, adriamycin, and mitomycin-c (fam) combination chemotherapy in the treatment of advanced gastric cancer

Thirty‐six patients with advanced measurable gastric cancer were treated with a new combination chemotherapy program consisting of 5‐fluorouracil, Adriamycin and mitomycin‐C (FAM). Fifty percent of patients achieved an objective partial response. The median duration of remission was 9.5 months and the median survival for responding patients was 13.5 months, with 2 remaining alive at 14 and 26 months. The median survival for nonresponding patients was 3.0 months and all were dead by 6 months after initiation of therapy. The median survival of all 36 patients treated with FAM was 5.5 months. An analysis of possible prognostic variables including initial performance status, resectability of the primary gastric tumor and histologic differentiation of the neoplasm failed to account for differences in patient response and survival. The FAM regimen was well tolerated, and produced only moderate bone marrow suppression. These results demonstrate that some patients with advanced gastric cancer can be effectively palliated with FAM chemotherapy. Phase III trials are warranted to assess the effect of the FAM regimen on the survival of patients with advanced gastric cancer.

Tetracycline and quinacrine in the control of malignant pleural effusions. A randomized trial.

Eighteen patients with advanced metastatic malignancy who had 21 pleural effusions requiring sclerosis for control were randomly allocated to intrapleural therapy with tetracycline or quinacrine. Tetracycline produced partial or complete control of the effusion in ten of 12 trials for a median duration of 6 months (range 1.5 to 22 months). Partial or complete control was obtained in nine of ten trials with quinacrine, for a median duration of 3 months (range 1 to 13 months). All complete responders who died achieved control of their effusions until their terminal admissions despite clinical evidence of overt systemic tumor progression in the intervening period. Single‐dose tetracycline therapy was accompanied by less fever (p < 0.04) and less pleuritic pain (p = 0.09) than quinacrine. Tetracycline is effective, well tolerated, easily administered, and should be considered as the initial therapy for malignant pleural effusions requiring pleural sclerosis.

Efficacy of tetrahydrocannabinol in patients refractory to standard antiemetic therapy

SummaryOral delta-9-tetrahydrocannabinol (THC), 15 mg/m2, was compared to prochlorperazine (PCZ), 10 mg. for the control of cancer chemotherapy-related emesis. Thirty-six patients whose vomiting was refractory to standard antiemetic therapy were entered in this randomized comparative cross-over study. THC decreased nausea and vomiting in 23 of 36 (64%) patients compared to 1 of 36 receiving PCZ. THC efficacy was not dependent on the class of antineoplastic-agent inducing the emetic symptoms, age of patients or type of sensorial change experienced. Using the 15 mg/m2 dose, all patients experienced transient sensorial changes, characterized as a pleasant “high” in 19 or a variable state of dysphoria in 17 cases. This study confirms the usefulness of THC in patients whose chemotherapy-induced nausea and vomiting is refractory to other standard antiemetics. While excellent antiemetic control was achieved at the dosage 15 mg/m2, dysphoria was encountered at this dose level and we recommend that an initial dose of 5 mg/m2 which, if necessary, can be carefully increased to achieve maximum antiemetic benefit.

Association of breast cancer with meningioma: report of two cases and review of the literature.

We report two cases of breast cancer in whom meningioma subsequently developed and provide a brief review of the literature. A hormonal interrelationship is suggested. The knowledge of this potential association is important in the interpretation and treatment of patients with breast cancer who develop central nervous system manifestations. Cancer 42:1992‐1994, 1978.

5‐fluorouracil, adriamycin, and mitomycin‐C (FAM) chemotherapy for adenocarcinoma of the lung

Twenty‐five patients with advanced measurable adenocarcinoma of the lung were treated with combination chemotherapy consisting of 5‐fluorouracil, adriamycin, and mitomycin‐C (FAM). Objective response (1CR, 8PR) was obtained in 36% of patients. The median duration of response was 7.0 months and the median survival for responders is greater than 8.5 months. Five responders are alive 5.5 to 23.5 months after starting therapy. Three of four patients evidencing stabilization of disease are alive at 10–23 months. Nonresponding patients had a median survival of 2.5 months and none lived beyond seven months. Tumor response and survival suggested correlation with initial performance status and limited disease. The FAM regimen was tolerated well, with moderate bone marrow suppression and gastrointestinal symptoms being the only clinically significant toxicities. These results indicate that patients with advanced pulmonary adenocarcinoma can obtain objective tumor regression with FAM chemotherapy.

Phase I studies on chlorozotocin.

A phase I investigation of chlorozotocin, a new‐water soluble chloroethylnitrosourea, was undertaken to define its pharmacologic effects in man. Forty‐three patients received single intravenous doses ranging from 5 to 175 mg/m2 every 6 wk. No signs of toxicity were observed at doses of under 120 mg/m2, but thrombocytopenia occurred at higher doses. The thrombocytopenic nadir appeared to be dose‐dependent and occurred 4 wk after treatment. Platelet transfusions were required in 2 patients who had previously received intensive chemotherapy. No significant leukopenia occurred. A mild reversible and delayed elevation of hepatic transaminases was found in 25% of courses of 120 mg/m2 or more. No renal toxicity was observed and gastrointestinal toxicity was mild. Investigation of clinical pharmacology revealed a rapid triphasic plasma clearance with initial t½s of 3, 15, and 30 min. The concentration of N‐nitroso intact drug at 1 hr was 10% of the initial peak level. Renal excretion accounted for half of the dose. No significant concentration of N‐nitroso intact or radiolabeled drug was detected in the cerebrospinal fluid of 2 patients in whom it was examined. There were objective signs of therapeutic activity in 5 patients, 3 of whom had melanoma. Based on these studies, the recommended dose for phase II investigation of chlorozotocin is 120 mg/m2 every 6 wk.

Spontaneous streptococcus pneumonia peritonitis in a patient with metastatic gastric cancer. A case report and etiologic consideration

Spontaneous peritonitis in adults has not been previously reported to occur in association with ascites of neoplastic origin. We report a patient with metastatic gastric adenocarcinoma in whom spontaneous streptococcus pneumonia peritonitis occurred as a terminal event. Massive metastases may have resulted in significant loss of the hepatic reticuloendothelial system and impaired the capability of the liver to function as an effective bacterial filter, predisposing the patient to bacterial peritonitis.

Chemotherapy of large intestinal carcinoma. Current results and future prospects.

Chemotherapy of advanced stages of large bowel cancer has until recently made little progress since the introduction of 5‐FU 16 years ago. While survival is improved for patients who respond, 5‐FU alone has made little impact on life span of the overall population of patients. Mitomycin‐C and the chloroethyl nitrosourea antitumor agents, and in particular methyl‐CCNU, have also demonstrated marginal activity in large bowel cancer. Two recently reported controlled clinical trials of combination chemotherapy have demonstrated response rates that are substantially better than those obtained with 5‐FU alone: a 43% response rate in colorectal carcinoma has been reported using a combination of 5‐FU, BCNU, vincristine, and DTIC, compared to a 25% response with 5‐FU as a single agent; a 44% objective response rate with a combination of 5‐FU, methyl‐CCNU, and vincristine has been reported to be significantly better than 5‐FU alone, 5‐FU as an adjuvant following surgical resection with curative intent has not prevented tumor relapse; however, it is hoped that future studies employing more effective drug combinations will result in increased numbers of patients achieving disease‐free survival.

Fast neutron irradiation for locally advanced pancreatic cancer

Abstract Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700–1750 neutron rad alone or in combination with 5-flourouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ration of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cacer was 6 months, which is less than that reported with 5-flouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemprrhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is controlled clinical trials.

Biology, Diagnosis, and Chemotherapeutic Management of Pancreatic Malignancy

Publisher Summary This chapter discusses the biology, diagnosis, and chemotherapeutic management of the exocrine and endocrine neoplasms of the pancreas. It is estimated that three-quarters of the nonendocrine malignancies of the pancreas are classified as duct cell adenocarcinomas. The remaining 25% are diagnosed as giant cell, microadeno, adenosquamous, mucinous, and anaplastic carcinomas. Only 1% of the tumors have been classified as acinar cell malignancies. There is considerable speculation as to the cell of origin of adenocarcinomas. Many pathologists regard the duct cell as precursor cell for the tumor. However, there is some evidence that acinar cells, under the stimulus of a carcinogen, can dedifferentiate to the ductal form of histology from which they arose embryologically. The clinical manifestations of adenocarcinoma of the pancreas have been reviewed, and it is clear that pancreatic cancer is rarely diagnosed at an early stage. The initial symptoms may be nonspecific and are frequently disregarded until anorexia, weight loss, pain or jaundice become overtly manifest. Anorexia and weight loss are common accompaniments of pancreatic cancer and may become the most debilitating features of the disease.