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Biomedical subjects

J U Gutterman

Publications and source records attributed to J U Gutterman.

At least 253 records · Page 14Linked to original sources

Nephrotoxicity from cancer immunotherapy.

Because systemic intravenous immunotherapy with Corynebacterium parvum is an effective immunopotentiating and immunotherapeutic agent in animals, clinical studies of this agent have been undertaken. Toxicities in man have been noted, but most are treated symptomatically. Three patients with metastatic melanoma developed oliguria, edema, diffuse bilateral pulmonary infiltrates, azotemia, hypoalbuminemia and hypocomplementemia, while receiving intravenous C. parvum therapy. All had renal biopsies that showed a proliferative glomerulonephritis with subendothelial basement membrane deposits. Immunofluorescence showed glomerular IgG, IgA, IgM, and the C3 component of complement. A fourth patient was found in retrospective chart review of 87 patients registered on two C. parvum-containing protcols. The frequency of the complication in this group was 3/87. Renal failure resolved in all four patients spontaneously after the cessation of C. parvum immunotherapy. Serial evaluation of renal function should be carried out in all patients on systemic adjuvant immunotherapy.

Adult↗

Phase 1 clinical investigation of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992), a new acridine derivative.

The compound 4'-(9-acridinylamino)methanesulfon-m-anisidide is a new derivative that was evaluated in a Phase 1 clinical trial. The schedule of drug administration consisted of daily i.v. injection for 3 consecutive days, repeated at 3-week intervals. Twenty-six patients received a total of 63 courses of 4'-(9-acridinylamino)methanesulfon-m-anisidide in a dose range from 4 to 50 mg/sq m/day. Hematopoietic toxicity was dose limiting, but it was of short duration and rapidly reversible. Mild nausea and vomiting were observed in 16% of the courses, and a mild degree of phlebitis was observed in 10% of the courses. Responses were observed in two patients with adenocarcinoma of the lung and one each of melanoma and acute myeloblastic leukemia. Phase 2 studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide are planned at a starting dose of 40 mg/sq m/day for 3 days in good-risk patients and at 25 to 30 mg/sq m/day for 3 days in poor-risk patients. Course of treatment would be repeated at 21-day intervals.

Acridines↗

Combination chemoimmunotherapy for extensive non-oat cell lung cancer.

In a prospective randomized trial, sc Corynebacterium parvum (C. parvum) immunotherapy did not significantly affect the responses and survival of 49 non-oat cell lung cancer patients receiving isophosphamide and adriamycin chemotherapy. Remissions (tumor regression greater than 50%) were seen in five of 23 patients receiving an intensive C. parvum schedule and in three of 26 patients receiving a nonintensive C. parvum schedule (22% versus 12%). Median survival was 20 weeks for patients given intensive C. parvum and 23 weeks for patients given nonintensive C. parvum. This study did demonstrate the importance of pretherapy immunocompetence, performance status, and weight loss as predictors for survival. Weight loss was the most significant prognostic factor. Performance status was closely associated with weight loss but skin reactivity to dermatophytin predicted independently and was the second most important prognostic characteristic.

Adenocarcinoma↗

Detection of immune complex-like materials in cancer patients' sera: a comparative study of results obtained with the C1q deviation and C1q binding tests.

In a collaborative study involving three laboratories, randomly coded sera from 47 patients and healthy donors were tested for soluble immune complexes by two versions of the C1q BT and by the C1q DT. Analysis of ranked data showed a close correlation between results obtained in all laboratories as well as good reproducibility on testing coded duplicate samples included in each panel of sera. However, with the use of values for normal donors established independently in each laboratory, the tests did not always agree in discriminating normal from abnormal sera, particularly with sera from cancer patients. Results reflected to some extent the methods used to inactivate the endogenous C1 complex in the test sera. Studies of 130 additional cancer patients revealed that 44 (34%) gave abnormal C1q BT values when inactivated with EDTA but only 35 (27%) were abnormal when heat inactivated (56 degrees for 30 min). Similarly 12 of 65 sera (18%) from patients with nonneoplastic diseases and 10 of 80 (13%) from healthy donors gave significantly abnormal results after addition of EDTA. Eight (12%) of the disease and six (8%) of the healthy controls' sera were similarly outside normal limits when heat inactivated. Repeated freezing and thawing of sera or changes in the concentration of PEG used to precipitate complex-bound 125I-C1q influenced C1q BT results more than duration of storage at -70 degrees C or changes ascribed to presence or absence of rheumatoid factors and CRP.

Antigen-Antibody Complex↗

Glycerol: a successful alternative to dexamethasone for patients receiving brain irradiation for metastatic disease.

Thirty-three patients with metastatic brain neoplasms of various types received glycerol instead of corticosteroids during periods of brain irradiation. In the 25 symptomatic patients, responses from this treatment were seen in those patients whose primary symptom was vomiting (ten of 12 patients), headache (nine of ten), papilledema (five of nine), paralysis (six of eight), confusion (six of seven), and dysphasia (four of six). Glycerol was well tolerated; it did not induce immunosuppression when administered in combination with radiotherapy and chemoimmunotherapy. Further investigation is indicated to compare its efficacy with that of dexamethasone.

Brain Neoplasms↗

Response of disseminated breast cancer to combined modality treatment with chemotherapy and levamisole with or without Bacillus Calmette-Guérin.

One hundred and fourteen evaluable patients with measurable metastatic breast cancer were treated with a combination chemoimmunotherapy program (5-fluorouracil, adriamycin, and cyclophosphamide [FAC-levamisole [LSM]). An additional 117 patients with similar characteristics were treated with the same program with the addition of bacillus Calmette-Guérin (BCG) by scarification (FAC-BCG-LMS). The results were compared to those observed in 44 evaluable patients treated with FAC chemotherapy alone. Overall remission rates were identical in the three studies (72%, 73%, and 72%). The median duration of remission was 9 months for FAC, 13 months for FAC-LMS (P = 0.07), and 14 months for FAC-BCG-LMS (P = 0.05). The median duration of survival was 17 months for FAC and 28.6 months for FAC-LMS (P = 0.01). Although the median survival for the FAC-BCG-LMS group has not been reached, it is significantly superior to FAC alone (P = 0.009). These three sequential studies suggest that the addition of nonspecific immunotherapy with LMS or the combination of BCG and LMS prolongs the duration of remission and survival of responding patients treated with chemotherapy. Combination immunotherapy with BCG and LMS did not seem superior to LMS alone in this study.

Adult↗

Histiocytic lymphoma in the brain as the only manifestation of relapse following remission maintainance with BCG immunotherapy.

This report describes an unusual case of lymphoma which, after 54 months of complete remission induced with chemotherapy and maintained with BCG immunotherapy, relapsed in the brain alone. It is possible that the immunotherapy led to this pattern of relapse: this is supported by several other studies. The difficulty in diagnosing brain lymphoma is emphasized.

BCG Vaccine↗

Adjuvant immunotherapy and chemoimmunotherapy in colorectal cancer (Dukes' class C): prolongation of disease-free interval and survival.

The poor postsurgical prognosis in patients with colorectal cancer of the Dukes' C classification has prompted a clinical trial of adjuvant immunotherapy versus chemoimmunotherapy intended to prolong either the disease-free interval or the overall survival or both. One hundred and twenty-one patients have been entered on this study. Fifty-two patients received BCG alone and 69 patients received the combination of 5-FU and BCG. The disease-free interval and the overall survival were compared with similar parameters in a group of historical controls with similar prognostic characteristics who were operated on in our institution prior to the initiation of the current study. There was no difference as yet between BCG alone and the combination of 5-FU + BCG in terms of both the disease-free interval and the survival. Both treatments, however, had significantly better results than the surgical controls. Adjuvant therapy, especially with BCG is advocated for patients with colorectal carcinoma, Dukes' C class, following potentially curative surgery.

BCG Vaccine↗

The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer.

Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.

Antibodies, Anti-Idiotypic↗

Phase 2 study with Baker's Antifol in solid tumors.

One hundred thirty-eight adults with advanced cancers were treated with Baker's Antifol. The complete response + partial response rate was only 10%. Best responses were obtained in 31 patients with lung adenocarcinoma (complete response + partial response, 13%), in 25 patients with colorectal carcinoma (partial response, 16%), and in 6 patients with renal cell carcinoma (partial response, 50%). Two partial responses occurred in 15 patients with squamous cancer. No significant responses were seen in 27 patients with other adenocarcinomas, 13 with sarcomas, 14 with melanomas, and 8 with miscellaneous tumors. The most frequent toxicities were dermatitis, stomatitis, gastrointestinal symptoms, and mild myelosuppression. The incidence of dermatitis was significantly decreased by shortening the schedule of Baker's Antifol administration from 5 to 3 days. Baker's Antifol has some degree of antitumor activity, and studies of combination of this agent with other effective chemotherapeutic agents are indicated.

Adenocarcinoma↗

Chemoimmunotherapy of advanced breast cancer: prolongation of remission and survival with BCG.

Forty-five patients with disseminated breast cancer were given a trial of combination chemotherapy consisting of fluorouracil, adriamycin, and cyclophosphamide (FAC) and immunotherapy with BCG given by scarification. The results were compared with those in a comparable group of 44 patients treated with FAC alone immediately before the chemoimmunotherapy study. The remission rates (73% and 76% for FAC and FAC-BCG respectively) were similar in both studies. The durations of remission for patients on FAC-BCG (medium 12 months) were longer than remissions achieved for patients given FAC alone (median 8 months) (P = 0.068). The most notable effect of BCG was on survival. Thus 21 out of 34 patients achieving remission on FAC-BCG were alive at the time of the last follow-up examination (median over 22 months) compared with 11 out of 32 patients achieving remission on FAC (median 15 months) (P = 0.01). Twenty-six of the 45 patients given FAC-BCG were alive at the time of the last follow-up examination (median over 22 months) compared with 12 of the 44 patients given FAC (median 15 months) (P = 0.005). Although the apparent benefit of BCG could be explained by a maldistribution of some prognostic factors, the data suggest that further trial of chemoimmunotherapy of breast cancer should be carried out.

Adult↗