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Biomedical subjects

M Rozencweig

Publications and source records attributed to M Rozencweig.

At least 73 records · Page 4Linked to original sources
PubMed1983

Phase I study of carboplatin given on a five-day intravenous schedule.

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.

Adult↗
PubMed1983

Clinical predictivity of transplantable tumor systems in the selection of new drugs for solid tumors: rationale for a three-stage strategy.

The purpose of this work is to analyze the strategy used for the discovery of potentially clinically effective drugs by means of transplantable tumor systems in mice. With the present strategy used by the National Cancer Institute and the European Organization for Research on Treatment of Cancer, most new compounds are initially tested in the P388 leukemia model. Drugs showing activity in this prescreen are subsequently evaluated in a panel of eight screens (B16, CD8, Co38, L1210, LL, CX-1, LX-1, and MX-1). Positivity in any one of these screens qualifies a new drug for further preclinical studies leading to phase I-II clinical trial. Our analyses of the experimental screening data for 1949 compounds, and the comparison of results in humans and mice for 69 drugs that have been clinically evaluated against solid tumors, have indicated that the correlation of screening and clinical results is low and that a modified approach using four systems (P388, B16, L1210, and MX-1) would have been sufficient to uncover most of the drugs presently shown to be clinically active. In order to take advantage also of the information provided by other screens of the panel, a three-stage strategy can be used. In the first stage, compounds would be tested in the P388 prescreen, with a slightly higher level of response being required (T/C% greater than or equal to 125 instead of 120). In the second stage, prescreen-positive drugs would be tested in the B16, L1210, and MX-1 systems. Drugs positive in any one of these screens may then be tested in Co38, LL, and CX-1 to determine priorities for clinical study. For new chemical structures of particular promise, this third stage could be dropped. LX-1 and CD8 are not useful in this context. Such a strategy would be much more economical and faster than the automatic use of nine systems, and the resultant savings should permit the discovery of an increased number of potentially active compounds.

Animals↗
PubMed1982

[Clonogenic cultures of human tumours. Experience and prospects in cancer chemotherapy (author's transl)].

Malignant cells grow selectively in semi-solid media. Cultures of single cell suspensions in these media result in the formation of colonies which are believed to represent clones of stem cells. Cells freshly sampled in cancer patients are assayed in such a system to quantitate the in vitro effect of various anticancer agents vs untreated controls. Partially retrospective comparisons between in vitro and in vivo data are very encouraging and suggest that observations in this assay correlate very favorably with clinical findings. This clonogenic assay should provide an experimental model of special relevance to clinical cancer chemotherapy and should greatly help define optimal treatments in individual patients. Although many technical problems remain to be settled, prospective studies are ongoing to determine to what extent the assay is actually predictive of the response to chemotherapy in cancer patients.

Antineoplastic Agents↗
PubMed1982

Combination of dacarbazine and mitomycin in advanced colorectal cancer.

Twenty evaluable patients with advanced measurable colorectal cancer received 3-week courses of a combination of IV dacarbazine 300 mg/m2/day from day 1 to day 5 and IV mitomycin 2 mg/m2/day from day 1 to day 5. Fourteen of these patients had had no prior chemotherapy and received two or more courses of this two-drug regimen. None of the patients achieved complete or partial response. Severe to life-threatening myelosuppression, was encountered in patients with prior radiotherapy and or prior chemotherapy, and/or in patients with a Karnofsky score less than or equal to 70. Hematologic toxicity was mild in the other patients. Nonhematologic toxic effects were generally mild to moderate and consisted essentially in nausea and vomiting. It is concluded that in our hands the regimen selected for this trial has no significant antitumor activity in advanced colorectal cancer.

Adult↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced breast cancer: a phase II trial of the EORTC breast cancer cooperative group.

Twenty-nine evaluable patients with extensively pretreated breast cancer received PALA, a new pyrimidine antimetabolite. The drug was given by intravenous infusion over 60 min, at a daily dose of 2.5 g/m2 for 2 consecutive days. Courses were repeated at 2-week intervals and doses were escalated to toxicity. Two objective partial remissions were observed, lasting for 3 and 4.5 months respectively. Toxic effects were dose-related and consisted mainly of mucocutaneous manifestations, i.e., skin rashes, stomatitis, diarrhea, conjunctivitis and corneal ulcerations. Evidence of antitumor potential in far-advanced disease and lack of myelosuppression point to the need for additional trials of PALA in a more favorable selection of patients with breast cancer.

Adult↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced soft tissue sarcoma: a phase II trial of the EORTC soft tissue sarcoma group.

Thirty-six patients with measurable or evaluable advanced soft tissue sarcoma were entered in a phase II trial with PALA. Among the 27 evaluable patients, 15 were men, the median age was 55 yr (16-69) and the median performance status (Karnofsky) was 80 (50-100). Most patients had leiomyosarcoma (8), liposarcoma (3), neurofibrosarcoma (3), synovial cell sarcoma (3), or undifferentiated sarcoma (3). Indicator lesions consisted essentially of lung metastases (21) and/or soft tissue lesions (14). All patients had received prior chemotherapy with 1-5 regimens and 6 had achieved objective response with these previous treatments. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-17) were administered. Partial remission (greater than 50%) was obtained in one patient with a liposarcoma who had also responded to prior combination chemotherapy. This single response to PALA lasted 6 weeks from initiation of therapy. Four patients had unchanged disease after 6+ courses of PALA and 22 had progressive disease. Toxic effects were generally mild to moderate and included cutaneous toxicity (17), diarrhea (14), stomatitis (13), ocular manifestations, consisting of conjunctivitis, corneal ulceration and/or photophobia (11), nausea and vomiting (6) and, possibly, seizures (2). There was no evidence of drug-related myelosuppression. It is concluded that PALA given at the dose schedule selected for this trial has no significant antitumor activity in advanced soft tissue sarcoma previously treated with chemotherapy.

Adolescent↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced malignant melanoma: a phase II trial of the EORTC Malignant Melanoma Cooperative Group.

Thirty-nine patients with measurable advanced malignant melanoma were entered in a phase II trial with PALA. Among the 36 evaluable patients there were 18 men and 18 women, with a median age of 53 yr (29-73) and a median performance status (Karnofsky) of 100 (50-100). Indicator lesion consisted essentially of soft tissue lesions (29 patients) and/or lung metastases (9 patients). Only three patients had received prior chemotherapy. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-8) were administered. Partial response (greater than 50%) was obtained in 4 patients for 6-17 weeks. Eight patients had stable disease after 3 courses of PALA and 24 had progressive disease. Toxic effects were generally mild to moderate and mainly included cutaneous toxicity, nausea and vomiting, stomatitis, and diarrhea. Myelosuppression was rare and negligible. It is concluded that PALA given at the dose schedule selected for this trial is fairly well tolerated and has borderline antitumor activity in good-risk patients with advanced malignant melanoma.

Adult↗
PubMed1982

Cisplatin and vindesine combination chemotherapy in advanced malignant melanoma: an EORTC phase II study.

Sixty-one evaluable patients with measurable advanced malignant melanoma received 4-week courses of a combination of cisplatin 100 mg/m2 as a 24-hr i.v. infusion on day 1 and vindesine 3 mg/m2 as an i.v. bolus on days 1, 8, 15 for two courses and every other week thereafter. Two patients achieved complete response for 46 and 81+ weeks respectively, eleven patients achieved partial response for a median of 17 weeks (range 8-26) and three patients had no change for 24 weeks or more. The overall response rate of 21% did not seem to be affected by prior chemotherapy or site of indicator lesions, soft tissue vs visceral. Myelosuppression, consisting essentially of leucopenia, required dose schedule modifications in 41% of the first two courses and 12% of the remaining courses, but never produced major complications. Non-hematologic toxic effects were prominent, especially nausea and vomiting, which were universal. Alopecia was seen in 71% of the patients, neuromuscular manifestations in 39%, diarrhea in 30%, renal impairment in 25%, mucositis in 12%, ototoxicity in 7% and phlebitis in 3%. These results do not suggest striking additive or synergistic antitumor activity of cisplatin and vindesine in advanced malignant melanoma, at least with the method of drug administration selected for this trial.

Adult↗
PubMed1982

Phase I clinical study of 9-hydroxy-2N-methyl-ellipticinium acetate (NSC-264137) administered on a 5-day i.v. schedule.

Twenty-three patients with advanced solid tumors received 9-hydroxy-2N-methyl-ellipticinium acetate at a single daily i.v. dose of 15-80 mg/m2 for 5 consecutive days, repeated every 3 weeks. One partial and one minor response were achieved in two patients with breast cancer. Dryness of the mouth was dose-related and dose-limiting. Local phlebitis was also dose-related and frequently severe at the highest dose levels. Other non-hematologic toxic effects were essentially mild to moderate and included nausea, vomiting, diarrhea, stomatitis, fever, weakness, transient renal and hepatic impairment, alopecia and chest pain. Minimal myelosuppression was encountered. It appears that 60 mg/m2/day is the maximum tolerated dose with a five-day schedule. According to our findings, this schedule does not seem to offer any advantage over the previously tested weekly administrations.

Adult↗
PubMed1982

The cardiotoxicity of anticancer agents.

It is clear from this review that a number of the antineoplastics cause or are associated with cardiotoxicity. Cardiotoxicity is not uncommon with the anthracyclines, but is rare for most of the other antineoplastics. With the use of anthracyclines earlier in patients' illnesses and in particular in adjuvant situations the clinical investigator must be constantly aware of the possible cardiotoxicity of those agents. Improved methods to detect cardiotoxicity before it is clinically apparent are sorely needed, particularly for this adjuvant group. The possibility of a chemotherapy induced cardiac disorder should always be entertained in the patient with cancer who develops a cardiac problem.

Antineoplastic Agents↗
PubMed1981

Clinical trials with the hexitol derivatives in the U.S.

Three hexitol derivatives, dibromomannitol (DBM), dibromodulcitol (DBD), and dianhydrogalactitol (DAG), originally investigated in Hungary, have been evaluated as anticancer agents in the United States. Their principal mechanism of action is attributed to alkylation via actual or derived epoxide groups. Their preclinical spectrum includes activity against murine leukemias and against the murine ependymoblastoma, which is particularly noteworthy for DAG. Dibromomannitol trials were targeted to chronic myelogenous leukemia but no advantage over busulfan therapy was demonstrable. Dibromodulcitol and DAG were sequentially evaluated for their usefulness against a wide variety of tumors. The activity of DBD against breast cancer has stimulated several continuing trials in this disease. On the other hand, DAG was disappointing in breast cancer and in several other malignancies, but some activity has been noted against lung cancer. Both DBD and DAG are being investigated for possible usefulness in the management of patients with intracranial neoplasms. The present clinical experience does not allow firm judgment on the advantage of one analogue over another. Such comparative analysis does point out the desirable direction of future studies as well as the limitations of current preclinical systems for the selection of analogues.

Animals↗