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Biomedical subjects

R Rosenbluth

Publications and source records attributed to R Rosenbluth.

11 recordsLinked to original sources
PubMed1991

A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma.

Conventional chemotherapy for unresectable or metastatic adenocarcinoma of the pancreas has had little effect on palliation or survival. Almost all studies of systemic therapy have involved empiric use of a variety of Phase II or conventional agents alone or in combination. On the basis of recent studies using a human tumor pancreatic cancer (PC) xenograft in nude mice, a Phase I clinical trial of cisplatin, high-dose cytosine arabinoside (Ara-C), and caffeine (CAC) was performed in patients with advanced incurable PC. A tolerable dose and schedule of the three agents were developed. Seven of 18 patients with measurable disease in this Phase I trial had partial responses to CAC. A Phase III comparison of CAC versus standard treatment using streptozotocin, mitomycin, and 5-fluorouracil (SMF) was performed. Eighty-two patients with advanced PC were entered into this random assignment trial. The two treatment arms were well balanced for the usual prognostic factors. Although the acute (e.g., nausea and vomiting) toxicities of CAC were greater than those of SMF, both groups of patients tolerated treatment resonably well. Ninety percent of patients were evaluable for response. Two patients (5.5%) on the CAC treatment arm (95% confidence interval [CI], 0% to 15%) and four patients (10.2%) on the SMF treatment arm (95% CI, 1% to 22%) had objective responses (partial response in measurable disease or improvement in evaluable disease). No complete remissions were observed. The 95% confidence limits of response for CAC and SMF overlapped. The median duration of survival for all patients on the SMF treatment arm was 10 months, although it was 5 months on the CAC treatment arm (P = 0.008). In this Phase III comparison, CAC was not superior to conventional therapy with SMF in terms of response and was inferior for survival. Neither regimen is effective treatment for advanced PC.

Adenocarcinoma↗
PubMed1990

Metastatic adenocarcinomas of unknown primary site. Prognostic variables and treatment results.

As part of a Phase II chemotherapy trial using mitomycin-C, adriamycin, and vindesine, 57 patients with adenocarcinoma of unknown primary site were assessed for prognostic variables predictive of response and survival. They were also evaluated for response and toxicity, usefulness of screening techniques, and eventual definition of primary site and pattern of progression. Only gender predicted response, with women being more likely to respond than men. Visceral metastases below the diaphragm, or the presence of liver metastases, predicted poor survival. Responding patients were highly likely to relapse first at sites of initial disease. Hemolytic-uremic syndrome was the most severe toxicity; other side effects were moderate. The response rate was 30% (three complete responders), which is similar to other current regimens. This study suggests that patients with better prognosis characteristics of single site of disease and without intraabdominal tumor may benefit from a policy of expectant observation after local control has been established. Patients with multiple sites of disease and/or intraabdominal tumor are appropriate candidates for investigational chemotherapy.

Adenocarcinoma↗
PubMed1990

Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer.

One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.

Adult↗
PubMed1989

Cisplatin and 5-fluorouracil infusion for metastatic colorectal carcinoma. Differences in survival in two patient groups with similar response rates.

Because of reported synergism between 5-fluorouracil (5-FU) and cisplatin (CDDP) in L1210 leukemic mice and activity of this combination in clinical studies, a trial was initiated in previously untreated patients with advanced colorectal carcinoma. Cisplatin at 20 mg/m2 and 5-FU as a continuous infusion at 1000 mg/m2 were both administered for 5 consecutive days every 4 weeks. Forty-one patients were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) and 46 were treated by the Community Clinical Oncology Program (CCOP) physicians. A 50% reduction in measurable disease was seen in 12 of 35 (34%) MSKCC patients and in nine of 41 (22%) of the CCOP patients with 95% confidence intervals of 0.18 to 0.50 and 0.10 to 0.35 in the two groups, respectively. The predominant toxicities were as follows: nausea and vomiting, 32%; mucositis, 26%; leukocyte counts less than 2000 cells/mm3, 17%; platelet counts less than 25,000 cells/mm3, 8%; and severe neurotoxicity, 5%. Dose attenuation was similar in the two groups. The median survival was 16.4 months for the MSKCC group and 9.6 months for the CCOP group (P = 0.0003). Although the baseline characteristics (age, sex, performance status, and baseline lactic dehydrogenase [LDH] and alkaline phosphatase) were similar, on further examination differences between the two groups were evident. In the MSKCC group, 14% of patients with liver metastases had greater than 50% of their liver involved with tumor whereas this occurred in 41% of the CCOP group (P = 0.03). The LDH values greater than 500 U/l were observed in 10% of patients in the MSKCC group and in 37% of the patients in the CCOP group (P = 0.007). Characteristics which reflect the bulk of disease, such as the percent of liver involvement, need to be analyzed in order to evaluate purported survival differences in randomized and nonrandomized trials of colorectal carcinoma.

Adult↗
PubMed1989

One good lesson.

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Expert Testimony↗
PubMed1987

Phase II trial of carboplatin in advanced malignant melanoma.

Twenty-six evaluable patients with metastatic malignant melanoma who had not received prior chemotherapy were treated in a phase II study with carboplatin (CBDCA), 400 mg/m2 iv every 4 weeks. There were five partial responses of 3, 3+, 5, 7+, and 12+ months' duration. Thrombocytopenia was the dose-limiting toxicity; ten patients had transient platelet count depressions to less than 75,000/mm3. Mild to moderate nausea and/or vomiting occurred in 15 patients. Renal, auditory, and neurologic toxic effects were not encountered. Since the response rate of 19% (95% confidence limits, 8%-38%) is similar to that noted for dacarbazine, carboplatin, singly and in combination with other agents, needs further evaluation in patients with malignant melanoma.

Adult↗
PubMed1972

Temperature-sensitive mutations in Drosophila melanogaster. IX. Dominant cold-sensitive lethals on the autosomes.

Ethyl methanesulfonate-treated autosomes were screened for the presence of dominant cold-sensitive (DCS) lethal mutations in Drosophila melanogaster. None was found among 6,552 treated and 168 untreated third chromosomes. Twenty-three DCS-L chromosomes which caused death at 17 degrees C but survived at 22 degrees C and 29 degrees C were recovered from 5,046 mutagenized chromosome 2's.-The DCS-L mutations all mapped around dp and appeared to be functionally allelic. Lethality of heterozygotes for most of the DCS-L's occurred over a prolonged interval from the embryonic through the larval instars. Prolonged incubation at 17 degrees C did not demonstrate any maternal effect on zygotic survival.

Age Factors↗