Search PubMed⌕ Search

Biomedical subjects

M Rozencweig

Publications and source records attributed to M Rozencweig.

At least 55 records · Page 3Linked to original sources

Combination chemotherapy with cisplatin, methotrexate, bleomycin, and vincristine (CABO) in advanced squamous cell carcinoma of the head and neck.

A combination of cisplatin, methotrexate, bleomycin, and vincristine (CABO) was assessed in advanced epidermoid head and neck cancer. Among 72 patients with recurrent or metastatic disease and measurable lesions, there were 9 complete and 27 partial responses for an overall response rate of 50%. These results were adversely affected by prior surgery plus prior radiotherapy. The median response duration was 28 weeks (16-100+) in complete responders and 16 weeks (6-84) in partial responders. CABO was also administered to 56 patients with measurable, previously untreated, locoregional disease. In these patients, complete and partial response rates were 18% and 46%, respectively. Toxic effects were generally mild to moderate. In spite of its encouraging therapeutic efficacy, CABO is unlikely to be clearly superior to single-agent chemotherapy, at least in recurrent or disseminated disease. Increased effectiveness of CABO given as initial treatment suggests that chemotherapy might play an effective adjuvant role in carefully selected patients.

Antineoplastic Combined Chemotherapy Protocols↗

Chemotherapy principles in the treatment of prostatic cancer.

The efficacy of chemotherapy for prostatic cancer is difficult to evaluate owing to the low incidence of measurable indicator lesions and the resulting need for indirect response criteria. Although complete regressions remain exceptional, a number of agents, eg, doxorubicin and cisplatin have been shown to be effective in the treatment of this disease. So far, combinations of effective agents with or without concomitant hormone therapy have not proven to be more effective than single agents. Androgen priming has considerable theoretical appeal and deserves further consideration. A higher effectiveness of chemotherapeutic agents might be obtained by linkage to various carriers. Estramustine phosphate is an example of such a complex that has a cytotoxic effect in test systems in which estrogen has no effect and in patients with hormone-refractory prostatic cancer. The use of hormonal and other carriers that could increase the specificity of chemotherapeutic agents deserves extensive exploration.

Animals↗

Phase II study of carminomycin in a human tumor cloning assay.

The anticancer activity of carminomycin was investigated in a human tumor cloning assay. No efficacy could be identified in the WiDr and the MCF7 cell lines which were highly responsive to doxorubicin. In addition, drug testing experiments were carried out in samples of various malignancies freshly obtained from 86 patients of whom 54 had not received prior anthracyclines. A reduction in the number of tumor colony forming units by 50% or more was seen in 1/26 breast cancers, 1/22 ovarian cancers and 1/7 melanomas. Cross-resistance studies indicated that eight tumors were responsive to doxorubicin only and one to carminomycin only whereas two were sensitive to both and 73 were resistant to both. This in vitro Phase II study corroborates the disappointing clinical results achieved with carminomycin.

Breast Neoplasms↗

Phase II study of 9-hydroxy-2N-methylellipticinium acetate.

A broad phase II trial of elliptinium was conducted in 105 evaluable patients with advanced solid tumors. The drug was given as a 60-90-min i.v. infusion at a weekly dose of 100 mg/m2. Of 36 breast cancer patients, one achieved complete and six achieved partial response for an overall response rate of 19%. Responses lasted for 12-56 weeks from initiation of therapy. There was also one partial response among 21 patients with squamous cell carcinoma of the lung. No response could be obtained in 17 patients with colon cancer, 13 patients with head and neck cancer and 18 patients with a wide variety of other malignancies. Myelosuppression was minimal. Nausea and vomiting were the most frequent toxic effects. The drug also produced serious xerostomia and acute intravascular hemolysis. Asthenia was common. Other adverse reactions included fever and chills, transient neurologic and cardiovascular manifestations and renal function impairment. Additional work is needed to define optimal modes of drug administration.

Adult↗

Phase II trial of epirubicin in advanced squamous, adeno- and large cell carcinoma of the lung.

Epirubicin , a stereoisomer of doxorubicin with suggested lower potential for cardiotoxicity in animal tumor systems, was evaluated in a disease-oriented phase II trial in non-small cell lung cancer. The drug was given as a direct i.v. injection of 90 mg/m2 repeated every 3 weeks. Four partial remissions were observed among 75 evaluable patients. Forty-two of the 75 patients had received no prior chemotherapy. The predicted true response rate is equal to 5% (0.2-10%). Leucopenia (75% of patients), gastrointestinal disturbances (76% of patients) and alopecia (53% of patients) were common side-effects observed. Four patients had cardiac abnormalities after treatment with epirubicin (one sinustachycardia , two premature beats, one biopsy-proven cardiomyopathy with congestive heart failure). One patient developed a peripheral neuropathy possibly related to epirubicin . We conclude that epirubicin in the present dose and schedule is an inactive agent in patients with non-small cell lung cancer.

Adenocarcinoma↗

Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer.

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.

Adult↗

Predictive tests for the response to cancer chemotherapy: limitations related to the prediction of rare events.

The reliability of a predictive test may be characterized by its sensitivity and specificity. The probability that a predicted event will actually occur depends on these indexes as well as the frequency of the predicted event. If such a test is used to predict for the therapeutic effect of single-agent chemotherapy in cancer patients, its predictive value is markedly affected by a generally low therapeutic efficacy in an unselected population.

Antineoplastic Agents↗

[Phase I study of alizapride in cancer patients treated with cisplatin].

Alizapride in a new methoxy-2 benzamide derivative with antiemetic properties. The dose-effect relationship of this compound was studied in 24 cancer patients treated with cisplatin regimens. Alizapride was administered as 15 min intravenous infusions at doses of 1 to 5 mg/kg repeated every 2 hours for 5 administrations. No adverse reactions were noted at doses of 1 to 3 mg/kg. Serious orthostatic hypotension was observed at the highest dose level. Other side effects were essentially mild to moderate and consisted of somnolence and diarrhea. The study indicated that the dosage level of 4 mg/kg is suitable for clinical use. The antiemetic activity of alizapride in patients receiving cisplatin therapy remains to be firmly established in a randomized study. This trial suggested a better antiemetic effect of alizapride in naive patients as compared to those previously treated with anticancer chemotherapy.

Adult↗

Phase I trial with 4'-deoxydoxorubicin (esorubicin).

4'-Deoxydoxorubicin is a new anthracycline derivative. Experimentally, the drug shows efficacy against doxorubicin-resistant malignancies and, as compared to the parent compound, it has reduced potential for heart damage. This Phase I trial was conducted with a single dose intermittent schedule. 4'-Deoxydoxorubicin was given by rapid i.v. administration at doses of 20, 30, 35 and 40 mg/m2. A total of 25 adult patients with a variety of solid tumors received a median of two courses (1-4). Leukopenia was dose-related and dose-limiting. Occasionally severe thrombocytopenia was also encountered. Nonhematological toxic effects were mostly mild to moderate and were qualitatively similar to those commonly reported with doxorubicin. The frequency of local reactions was apparently increased but the incidence of alopecia and gastrointestinal distress was noticeably lower. There were no acute or chronic drug-induced cardiac effects. Antitumor activity was suggested in a patient with a carcinoma of the cardia. For Phase II trials, doses of 35 and 30 mg/m2 every 3-4 weeks may be recommended in good-risk and poor-risk patients, respectively.

Adult↗

Clinical phase I trial of marcellomycin with a single-dose schedule.

Marcellomycin is a new anthracycline that was proposed for clinical trials on the basis of experimental data suggesting reduced potential for hematologic and cardiac toxicity as compared to conventional anthracyclines. This phase I trial was designed to determine the maximum tolerated dose of marcellomycin at a single-dose schedule. The drug was given as a 15-to 30-min i.v. injection. Eighteen patients with a variety of solid tumors received a median of 2 courses (range: 1-5) at doses of 5-60 mg/m2. Myelosuppression was dose-limiting and somewhat unpredictable. It was characterized by early thrombocytopenia and late leukopenia. It occurred at doses greater than or equal to 40 mg/m2 and resulted in a few cases of infection and hemorrhage. Nausea, vomiting and stomatitis were frequent and occasionally severe. Other common non-hematological toxic effects consisted of local phlebitis and fatigue. Electrocardiographic changes were also encountered. Hair loss was rare and negligible. No antitumor activity could be detected. It appears that phase II trials should be preferably restricted to ambulatory patients and that a dose schedule of 50 mg/m2 repeated every 3 weeks may be proposed for this favorable patient population.

Adult↗

Phase II study of amsacrine in solid tumors: a report of the EORTC Early Clinical Trial-Group.

A total of 239 patients with advanced solid tumors were treated in this phase II trial. Amsacrine was administered as a single i.v. dose of 120 mg/m2 repeated at 21-day intervals. The initial dose was reduced to 90 mg/m2 in the case of extensive prior therapy. Some antitumor activity was detected in head and neck cancer but the drug appears to lack significant efficacy in epidermoid lung cancer as well as in carcinoma of the breast, melanoma, renal cell cancer, colorectal cancer and non-seminomatous testicular cancer. Leukopenia was the major toxic effect encountered in this trial and was similar at 90 and 120 mg/m2.

Adult↗

Phase II trial of diaziquone (AZQ) in advanced malignant melanoma.

Forty-two evaluable patients with malignant melanoma received AZQ 27 mg/m2 i.v. every 4 weeks. In 5 patients with poor marrow reserve this dose was reduced to 20 mg/m2. Doses were rapidly escalated when no significant myelosuppression was encountered in previous courses. Twenty-five patients had received no prior chemotherapy. A single partial response was obtained for 3 months. Inconsistent myelosuppression was the main toxic effect in this trial. The median WBC and platelet nadirs were 3200/mm3 (900-19,500) and 105,000/mm3 (33,000-530,000) respectively. In 2 patients leukopenia was complicated by a transient episode of infection. One-third of the patients did not experience significant myelosuppression. Non-hematologic adverse reactions were generally mild to moderate and consisted of nausea and vomiting in 26 patients and alopecia in 1. It is concluded that at this dose schedule AZQ is ineffective against malignant melanoma.

Adult↗