Biomedical subjects
Publications and source records attributed to W Regelson.
Twenty-five patients with a variety of solid tumors were treated with hydrazine sulfate. Hydrazine was given orally in the form of 60 mg capsules from one to four times daily. No patient had a 50% reduction of tumor size. Subjective benefit was seen in three patients but it was of brief duration.
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Pyran copolymer (maleic anhydride-divinyl ether) has consistently reproducible molecular weight-related biologic effects associated with toxic, immunologic antitumor, and antiviral effects. Fortunately, the antitumor action occurs with the least toxic lower molecular weight fraction. Immunoadjuvant effects with this fraction would be critical to its development. Studies of polymers should include evaluation of effects on splenomegaly, splenic esterase changes, lipolysis, reverse transcriptase, nucleases, calcium flux, cyclic nucleotides, and complement and clotting elements.
This report is the result of an Eastern Cooperative Oncology Group (ECOG) study. Four hundred and 15 patients with inoperable metastatic malignant melanoma, excluding those with cutaneous metastases only, were randomized to one of three drug treatments: DTIC alone, methyl-CCNU alone, or the combination DTIC plus methyl-CCNU. Responses were seen in 14% of DTIC patients (19/127), 15% of methyl-CCNU patients (18/119) and 14% of DTIC plus methyl-CCNU patients (18/122). Duration of response was the same (14 weeks) for all three treatment groups. There was no difference among the treatments in achieving complete responses. Survival was improved significantly for responders (50 weeks) compared with nonresponders (15 weeks) regardless of treatment regimen. Toxicities were generally tolerable. DTIC caused significantly more gastrointestinal toxicity than methyl-CCNU. Methyl-CCNU caused significantly more bone marrow toxicity than DTIC. There were three drug-related deaths. All occurred in patients on combination DTIC plus methyl-CCNU. Important pretreatment characteristics that favor response are ambulatory status, female, less than 50 years old, no prior chemotherapy and no liver or brain metastases. Patients with favorable characteristics combinations had a 30% response rate, while those with unfavorable characteristic combinations had only a 9% response rate.
Autologous leukocytes (10(7) to 10(9)), obtained with the Haemonetic's Leukaphoresis apparatus, were inoculated directly into recurrent glioblastoma tumors via indwelling catheters or by direct intratumoral injection through existing craniotomy openings. The rational use for autologous leukocyte (lymphocyte) infusions was based on in vitro autologous lymphocyte cytotoxicity to glioblastoma cells in the absence of serum inhibitory factors. Seven of 17 patients treated had life expectancy under 1 month; all patients had received definitive surgery, and all but two received radiation, nitrosourea chemotherapy and/or dexamethasone, and showed evidence of clinically recurrent disease. Following autologous leukocyte infusion (lymphocyte/granulocyte ratio 1:1), eight patients sustained clinical improvement and were alive up to 17 months later. No neurotoxicity ascribable to the procedure has been observed. One patient, who was comatose at the time of single leukocyte infusion, returned to full activity and lived for 17 months without an increase in tumor mass by brain scan. These results suggest that infusions of autologous leukocytes (lymphocyte-monocytes) directly into glioblastoma may be a viable additional treatment for glioblastoma and certainly warrants further evaluation.
Twenty-three patients with malignant mesothelioma are described as to mode of presentation, symptoms, method of diagnosis and histology, Beginning in 1972, 10 patients were treated with drug combination including Adriamycin, Dacarbazine (DTIC), Cytoxan, and vincristine. Median survival of these patients was 9.5 months. Twelve patients who were treated with other modes of therapy had a median survival of about 4.75 months. One patient died after 22 days in the hospital, for whom a diagnosis was made at autopsy. While historical retrospective controls involving 13 patients are of limited value in assessing the usefulness of a new treatment, the authors feel that combination chemotherapy in 10 patients has shown enough activity to warrant further study. In addition, wide local resection, where possible, probably increases survival.
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This prospective randomized Eastern Cooperative Oncology Group (ECOG) study (1071) was designed to compare a new and promising cytotoxic agent TIC Mustard (triazeno imidazole carboxamide mustard, NSC 82196) with DTIC (dimethyl triazeno imidazole carboxamide, NSC 45388) in the treatment of inoperable melanoma. One hundred and seventy-eight patients were randomized to receive either DTIC (150 mg/m2/day X 5) or TIC Mustard (800 mg/m2/day X 5). Of this group 145 patients were evaluable for tumor response at the completion of the study. Objective responses were seen in 15/79 (19.0%) DTIC patients and 4/66 (6.1%) TIC Mustard patients. Adjustment of crude response rates yielded final response rates of 18.2% for DTIC patients and 5.8% for TIC Mustard. These differences were significant at the p less than or equal to .03 level. Median response duration was 15 weeks for the DTIC responders and 4 weeks for the TIC Mustard responders. Responders and nonresponders did not differ significantly in any of the standard prognostic categories. However, responders had a significantly longer median survival (47.5 weeks) compared to that for nonresponders (17.8 weeks). Toxicity was tolerable for either drug and no deaths were ascribed to either. We conclude that TIC Mustard has limited usefulness in the treatment of malignant melanoma and is less effective than DTIC.
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Several new "dual antagonists" were synthesized in which the 2,2-dimethyl (or ring C unsubstituted) aziridine phosphinyl function is linked to N-hydroxyurethane rather than the urethane moiety. Three of the new compounds showed very high activities against leukemia L1210 in mice.
A combined intraoperative and postoperative adjuvant program of 5 minus Fluorouracil (5 FU) for patients undergoing "curative" resection for adenocarcinoma of the colon and rectum was initiated as a randomized clinical trial in January 1968. Patients at the Medical College of Virginia and the University of Virginia were randomly assigned to an intraluminal 5 FU or intraluminal control (Saline) group and were so treated at the time of surgical resection if findings at operation indicated that all gross neoplastic disease could be resected. Patients with operative findings denoting incurability were eliminated from the study after surgical exploration. Those patients receiving intraluminal 5 FU (30mg/kg) received intravenous 5 FU (10mg/kg) on each of the two first postoperative days and 5 subsequent postoperative courses of oral 5FU (90 mg/kg in each 18 day course) over a one year period. By December 31, 1973 (6 years) 156 patients undergoing "curative" resection were entered into the study. SU therapy with the control or "No Treat" group reveal no significant benefit from this intensive adjuvant course of 5 FU thus far. Continued assessment of these patient groups and their subgroups will be required to develop confidence in these findings but the data thus far suggest no potential benefit from this particular adjuvant program.
53 patients with intractable malignant diseases that were treated with a new alkylating agent, 4-N,N-bis (2-chloroethyl) amino phenyl N (P-carboxyphenyl) carbanate, also knows as 'IC-140' were evaluated. The records of an additional 41 patients entered on this study could not be assessed from the standpoint of toxicity. At the dose level of 150 mg/m2/week, severe leukopenia (less than 2,000) and thrombocytopenia ( less than 75,000) were encountered in 23 of 34 patients. On the other hand, at the 100 mg/m2/week dose level, the severe toxicity was reduced to 8 out of 19 patients. Tumor response was evaluated in 43 patients. The overall response was 23% (29% at the 150 mg/m2, 13% at the 100 mg/m2) and the duration of the response varied from 3 to 32 weeks with a mean duration of 13 weeks. Responses were noted in patients with ovarian, renal, lung, hepatic, breast carcinomas and lymphosarcoma.
Ethyl-N-bis (2,2-dimethylethylamidinophosphoro) carbamate (AB-132) has been shown to potentiate the effect of whole-body radiation on inhibition of splenomegaly induced by Friend leukemia virus in ICR/H Swiss mice. The combined effect of AB-132 and radiation does not appear to be related to Friend virus inhibition but seems to act on the proliferating tumor in the spleen. Nine children with advanced cancer were treated with combined administration of local radiation and systemic AB-132. Although regression of tumor was seem, no dramatic effect on survival was apparent. One case of metastatic Ewing's sarcoma showed systemic tumor response to AB-132 in addition to localized response to radiation. Bone marrow depression appeared to be the main side effect of combination therapy.