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Biomedical subjects

J A Gottlieb

Publications and source records attributed to J A Gottlieb.

At least 19 recordsLinked to original sources
PubMed1979

Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia.

Piperazinedione was administered to 79 patients with solid tumors on an intermittent schedule with single doses of 1.5-36 mg/m2. Courses were usually repeated at 4-week intervals. Twenty-five patients with leukemia were treated at doses of 18-36 mg/m2 (occasionally for 2 successive days) every 1-4 weeks. Of 48 evaluable patients with malignant melanoma, three (6%) achieved partial remission and nine (20%) had stable disease. Eight of 17 (47%) patients with adenocarcinomas and one of two (50%) patients with lymphomas also had stable disease. Six of 14 (43%) patients with acute myelogenous leukemia showed hematologic improvement, as did one of 11 (9%) patients with blast cell crisis of chronic myelogenous leukemia. The principal toxic effect was myelosuppression, which occurred in 69% of the patients with solid tumors. Profound bone marrow aplasia occurred in 19% of the patients, resulting in six deaths (8%). Risk factors for marrow aplasia included extensive prior therapy, prior nitrosoureas, cumulative toxicity from piperazinedione, and abnormal liver function tests. The recommended doses for further studies are 9 mg/m2 for patients with risk factors for marrow aplasia, 12 mg/m2 for patients with prior therapy, 15 mg/m2 for previously untreated patients, and 24-36 mg/m2 for patients with acute leukemia.

Adult↗
PubMed1978

Chemotherapy for squamous carcinoma of the cervix: doxorubicin--methyl CCNU.

Treatment was initiated for metastatic or recurrent squamous carcinoma of the cervix with a combination of doxorubicin and methyl CCNU in 37 patients. Results after at least one full course of chemotherapy were fully evaluated in 31 of these patients. The objective response rate of 45.1 per cent obtained with this therapy compared favorably with those obtained by other authors using single or multiple agents. This chemotherapy regimen may need to be modified to improve patients' tolerance. The improved survival rate and high number of complete remissions demonstrated in this pilot study show promise for this type of chemotherapy in the future.

Adult↗
PubMed1978

QRS voltage change with adriamycin administration.

A decrease in the electrocardiographic limb lead QRS voltage of greater than or equal to 30% was highly correlated with the development of congestive heart failure in patients treated with adriamycin (ADM). It is felt that if a decrease in limb lead QRS voltage greater than or equal to 30% were detected in a patient receiving ADM, cardiomyopathy might be avoided or ameliorated by discontinuation of the drug.

Adolescent↗
PubMed1977

Adriamycin cardiomyopathy--risk factors.

The records of 53 patients treated with Adriamycin, 17 of whom developed congestive heart failure and 36 of whom received a similar total dose of Adriamycin without developing congestive heart failure, were analyzed for factors associated with Adriamycin cardiomyopathy. The risk of cardiomyopathy was significantly greater in patients who developed a larger than or equal to 30% decrease in limb-lead QRS voltage. Concurrent cyclophosphamide and mediastinal radiotherapy lowered the cumulative Adriamycin dose necessary for the development of cardiac toxicity. Uncontrolled hypertension also appears to be a risk factor in potentiating the development of Adriamycin cardiomyopathy at lower doses. Congestive heart failure was more likely to be fatal if it developed shortly after the last dose of Adriamycin. These findings can be utilized to increase the safety of Adriamycin therapy in the future.

Adolescent↗
PubMed1977

Clinical evaluation of Asaley.

Asaley is an L-leucine derivative of sarcolysin which is more active against some rodent tumors. Studies in the USSR demonstrated activity in patients with ovarian and breast carcinoma, Hodgkin's disease, and multiple myeloma. This study in 73 evaluable patients indicated that an appropriate oral dose for patients with adequate bone marrow is 800 mg/M2/day X 4 days at 5-6 week intervals. The most common toxicities were myelosuppression, nausea, and vomiting. Antitumor activity was observed in 2 of 24 evaluable patients with melanoma, and stabilization of previously progressive disease was observed in patients with adenocarcinoma of the colon, multiple myeloma, lymphoma, breast carcinoma, and thyroid carcinoma. Responses were minimal and of short duration but most of the patients had received extensive prior therapy.

Adenocarcinoma↗
PubMed1977

Treatment of metastatic germ-cell tumors in men with adriamycin, vincristine, and bleomycin.

Twenty-five patients with metastatic germ-cell tumors were treated with a combination of adriamycin, vincristine, and bleomycin. Fifteen patients (60%) had previously received radiation therapy, chemotherapy, or both. Twenty patients (80%) responded to treatment, with eight (32%) patients achieving a complete remission (CR) and 12 (48%) patients achieving a partial remission (PR). The median duration of response for the patients with PR was 4 months, whereas four patients with a CR remain alive without evidence of disease for greater than 3 years after the initiation of treatment. Responses were observed in all tumor categories and apparently were not influenced by prior therapy. Side effects included gastrointestinal toxicity, alopecia, neuropathy, skin changes, mucositis, and myelosuppression (more severe in previously treated patients). Though moderate success was demonstrated for this chemotherapy regimen, it does not appear as effective as more recent regimens including vinblastine and bleomycin.

Adolescent↗
PubMed1976

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↗
PubMed1976

Improved chemotherapy for small-cell undifferentiated lung cancer.

Bleomycin sulfate, doxorubicin hydrochloride, cyclophosphamide, and vincristine sulfate combination chemotherapy was given to 29 patients with small-cell undifferentiated lung cancer. Only four of these patients had limited disease, and in these patients there was 100% complete remission; two of these four patients remain in complete remission at more than 52 and 60 weeks. Of the 25 patients with generalized disease, 18 (72%) had neoplasm regression (greater than 50%), including two with complete remission (8%). The median duration of remission was 25 weeks. The median survival time from diagnosis was 39 weeks and that from initiation of therapy, 35 weeks. The drug regimen was well tolerated, and although substantial leukopenia was produced, there were only three patients in whom granulocytopenic infections developed. There was only one drug-related death.

Aged↗
PubMed1976

BACON (bleomycin, adriamycin, CCNU, oncovin and nitrogen mustard) in squamous lung cancer. Experience in fifty patients.

Fifty patients with inoperable squamous carcinoma of the lung. 38 with extensive, and 12 with limited disease, were treated with BACON. Tumor regression greater than 50% was observed in 17 patients (45%) with extensive, and four patients (33%) with limited disease. Stabilization of disease for greater than or equal to 8 weeks was seen in four extensive and eight limited patients, and had the same prognostic importance with regard to survival as response: in extensive disease, responding and stable patients had median survival (MST) of 26 weeks from start of therapy, while MST for non-responders was 9 weeks. MST in limited disease (all patients responding or stable) was 32 weeks. Analysis of survival in extensive disease by performance status showed improvement in each category over historical control results for supportive care alone. BACON was better tolerated and probably more effective when CCNU was given every 8 weeks, rather than every 4 weeks.

Bleomycin↗
PubMed1976

Phase II evaluation of bleomycin. A Southwest oncology Group study.

Bleomycin given intravenously (i.v.) or intramuscularly (i.m.) in twice-weekly doses of 10 mg/m2 was evaluated for efficacy and toxicity in 382 patients. Responses were observed in 11/27 Hodgkin's diseases, 10/30 lymphomas, 9/22 squamous cell cancers of ectodermal origin, 12/26 germinal cancers, and 3/8 renal adenocarcinomas. The i.m. route is less likely to casue pulmonary toxicity or hypotension than the i.v. route. Advanced age and total doses exceeding 200 mg were associated with a higher risk of lung toxicity. All responders had shown at least improvement upon receiving 200 mg; higher total doses should be used only in responding patients.

Adenocarcinoma↗
PubMed1976

Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma.

Combination chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone) and HOP (Adrimycin, vincristine, and prednisone, was used as treatment for patients with pathologically staged, advanced non-Hodgkin's lymphoma. Among 204 evaluable patients treated on CHOP there were 71% complete remissions with 92% overall responses. Among the 216 evaluable patients on HOP there were 61% complete remissions and 88% responses. Complete remission rates among patients with histiocytic lymphoma were comparable to those of patients with lymphocytic disease. Patients with nodular lymphoma had higher rates of complete remission than their counterparts with diffuse lymphoma. This was noted with both CHOP (78% vs. 67%) and HOP (67% vs. 60%) induction therapy. Rapid responses were common, as more than 14% of complete remissions and 66% of overall responses were achieved with the first course of treatment. Patients in complete remission have been maintained with either cyclophosphamide, vincristine, and prednisone (COP) or arabinosyl cytosine, vincristine, and prednisone (OAP). After 1 year, 86% of patients on COP and 80% on OAP are projected to be free of disease.

Cyclophosphamide↗
PubMed1976

A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells.

The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.

Amphotericin B↗
PubMed1976

Clinical evaluation of ftorafur (pyrimidine-deoxyribose n1-2'-furanidyl-5-fluorouracil).

Ftorafur, a possible sustained-release formulation of 5-fluorouracil, was administered to 27 patients with metastatic cancers. The majority of patients had adenocarcinoma, most of which (60%) arose from the gastrointestinal tract. Ftorafur was given i.v. at doses ranging from 1 to 3 g/sq m/day for 5 days, repeated every 2 to 3 weeks. Gastrointestinal (68%) and neurological (17%) toxicities were the most common side effects encountered in this study and became dose limiting at doses greater than 2 g/sq m/day for 5 days. Myelosuppression (7%) was infrequent. Other toxicities included weakness (20%), chills and fever (8%), and phlebitis (1%). Of 24 evaluable patients, 4 (17%) responded (1 complete and 3 partial remissions). Responses were seen in 1 of 8 carcinomas of the lung, 1 of 5 carcinomas of the stomach, 1 of 3 carcinomas of the colon, and 1 of 1 carcinoma of the jejunum. The duration of response ranged from 4 to 58 weeks. The results of this study resemble somewhat those obtained with the laborious 5-day continuous i.v. infusion of 5-fluorouracil. Daily doses of 2 g/sq m for 5 days, repeated every 3 weeks, produced significant antitumor effect and tolerable toxicity.

Adenocarcinoma↗