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Biomedical subjects

M Perloff

Publications and source records attributed to M Perloff.

At least 37 records · Page 2Linked to original sources

High dose methotrexate followed by citrovorum factor reversal in patients with advanced cancer.

High dose methotrexate followed by citrovorum factor reversal has been utilized in twenty-six patients with advanced cancer. Four of 10 patients with head and neck cancer had an objective response. One of 7 patients with metastatic osteosarcoma to the lungs had stabilization with twenty treatments over 23 months. One patient with acute lymphocytic leukemia developed marrow aplasia but did not attain remission. The regimen was well tolerated when meticulous attention was paid to hydration, urine alkalinization, renal function and third space fluid accumulation. Life-threatening or lethal toxicity was encountered when these phenomena were not scrupulously observed.

Adolescent

Vinblastine, adriamycin, thiotepa, and halotestin (VATH): therapy for advanced breast cancer refractory to prior chemotherapy.

Nineteen postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy were treated with monthly cycles with the combinations of vinblastine, adriamycin, thiotepa and halotestin. Ten patients (52%) responded with a greater than 50% regression of measurable tumor. The median duration of response was 11.5 months, with 5/10 patients still responding at a mean follow-up of 10 months. Only 2/10 responders have died with a mean follow-up of 13.8 months. In contrast, 8/9 nonresponders have died (median survival 6.0 months). Response to therapy was neither influenced by site of disease, time interval from diagnosis to primary chemotherapy nor duration of response to primary chemotherapy. No patient was hospitalized because of drug induced toxicity. This combination of drugs is a tolerable effective regimen for patients relapsing after adjuvant chemotherapy or after primary combination chemotherapy for grossly metastatic disease.

Adult

Hepatocellular carcinoma in a young woman with prolonged exposure to oral contraceptives.

A case of hepatocellular carcinoma in a young female is presented in which the apparent etiology was the use of oral contraceptives for 5 1/2 years. Sequential therapeutic trials with intraarterial 5-fluorouracil, intraarterial adriamycin, and intravenous 1,3 bis[2-chloroethyl]-1-nitrosourea (BCNU) were unsuccesful. The adverse effects of oral contraceptives on the structure and function of hepatic tissue are reviewed.

Adult

Surgical adjuvant chemotherapy.

The evidence that the principles of surgical adjuvant chemotherapy developed in experimental animal systems also apply to a variety of neoplastic diseases in man has been clearly demonstrated. Micrometastatic disease can be eradicated with effective chemotherapy in several diseases. Prolongation of disease-free interval, if not cure, is now possible in diseases in which curative surgery alone or in combination with radiotherapy does not achieve these goals. The previously fatal childhood solid tumors--Wilms', Ewings' sarcoma, embryonal rhabdomyosarcoma--are curable in a high percentage of patients appropriately treated with combinations of surgery, radiotherapy, and chemotherapy. The prolongation of the disease-free interval in osteogenic sarcoma has permitted consideration of entirely new surgical approaches for this tumor in which radical amputation has traditionally been employed. The spectacular results achieved in the treatment of Stage II breast cancer may potentially save hundreds of thousands of lives in the coming decade. Clinically recognizable metastatic disease is rarely curable by any currently available treatment modality. The prolongation of disease-free intervals and production of cures when surgical adjuvant chemotherapy is employed may be partly explained by relatively more circulation, and thus drug delivery to each tumor cell, more favorable cellular kinetics, and a healthier and more immunocompetent host who is better able to withstand drug effects on normal tissues, and to participate in tumor destruction. Cures of certain patients with neoplastic diseases using surgical adjuvant chemotherapy has increased the incentive to learn more about new and old drugs and their effective use alone and in combination. Chemotherapy, in appropriate combinations with surgery, radiotherapy, and immunotherapy, may well be more efficacious in many clinical situations than the traditional use of single-modality treatment. The data presented in this paper relate solid evidence that the possibility of cure in a variety of neoplastic diseases is real.

Adult

Effects of methanol extraction residue of Bacillus calmette-Guérin in humans.

Forty patients with histologically confirmed neoplastic diseases were treated with the methanol extraction residue of Bacillus Calmette-Guérin (MER). Thirty-six received concomitant chemotherapy. MER was initially given intradermally twice a month, 1 week apart, at a dose of 200 mug into each of five sites draining different lymph node-bearing areas on the anterior body surface. Thirty-seven patients developed local ulcerations at least 0.5 cm in diameter at MER injection sites. Typical lesion evolution was characterized by erythema and induration followed by vesicle formation and central necrosis. Either granulation tissue or a thick nonulcerated eschar preceded healing, leaving a linear, flat scar. Systemic toxicity consisted of malaise, fever, and myalgias on the day of MER administration. No hematological or biochemical changes directly attributable to MER were observed. Dose titrations in decreasing 10-fold dilutions in a linear array in a single anatomical region were carried out on 35 occasions. All patients but three developed at least a 5-mm induration to the 1-mug dose within 2 weeks of titration. Dose reductions were necessary in 19 instances. The minimal dose that produced a 1-cm inflammatory lesion with central necrosis was 0.01 mug. Serial biopsies were performed. These indicated a time-related series of changes from a nonspecific inflammatory lesion to an acute inflammatory response with microabscesses, followed by noncaseating granulomata and ultimately fibrosis. MER is a quantifiable nonviable immunostimulant that obeys dose-response relationships in its cutaneous lesions.

Antineoplastic Agents

Combination chemotherapy with adriamycin and cis-diamminedichloroplatinum in patients with neoplastic diseases.

Forty-eight patients with a variety of advanced solid tumors were treated with a combination of adriamycin 50 mg/m2, and cis-diamminedichloroplatinum 50 mg/m2, every 2 to 4 weeks. Fifteen patients responded with a greater than 50% regression of measurable tumor; six with lung cancer; one, carcinoma of the breast; one, ovary; one, cervix; one, prostate; one, testis; one, maxillary sinus; and one, salivary gland, plus one patient with chemodectoma and one with adenocarcinoma of unknown primary. Responses lasted 1 to 18 months, with a median of 6 months. An additional six patients, including two with adenocarcinoma of the lung three with carcinoma of the cervix, and one with embryonal cell testicular carcinoma improved (25-50% regression of the tumor). Toxicity encountered included myelosuppression, azotemia, alopecia, nausea, vomitting, and stomatitis. Severe hematologic toxicity occurred only in those with compromised marrow function or with concurrent active hepatitis. Major potentiation of toxicity by the combination does not appear to have occurred.

Adolescent

Combination amphotericin B-rifampin therapy for pulmonary aspergillosis in a leukemic patient.

Pulmonary aspergillosis developed in a 62-year-old man with acute myelogenous leukemia. Therapy with amphotericin B and 5-fluorocytosine was begun. Synergy between amphotericin B and rifampin was demonstrated in vitro, and therapy with firampin replaced 5-fluorocytosine. Progressive clearing of the pulmonary lesion ensued, suggesting in vivo efficacy as well. Further studies of patients utilizing this regimen are warranted.

Amphotericin B

Phase I study of iv administration of methanol extraction residue of Bacillus Calmette-Guérin.

Four weekly iv doses, ranging from 10 to 640 microgram/m2, of the methanol extraction residue of bacillus Calmette-Guérin (MER) were given to 22 patients with advanced cancer in an effort to determine a maximum tolerated dose. Fever and chills for 24-48 hours were common at doses greater than 80 microgram/m2 but were prolonged for 3 days to 9 weeks at 640 microgram/m2. While moderate decreases in pulmonary vital capacity were seen at all dose levels, diffusing capacity decreased consistently only at higher doses. However, no roentgenographic changes suggestive of multiple lung granulomas were observed, such as were produced in dogs and mice by iv administration of MER. Autopsy failed to reveal granulomas in three patients. There were no objective tumor responses, nor were consistent changes observed in blood counts or skin tests to recall antigens. MER can be given iv with acceptable acute toxicity in doses up to 640 microgram/m2, at which point fever may be unduly prolonged. Patients given MER iv must be followed carefully for the development of interstitial pneumonitis.

Adult