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Biomedical subjects

R L Comis

Publications and source records attributed to R L Comis.

At least 55 records · Page 3Linked to original sources
PubMed1991

Pharmacologic study of etoposide and cisplatin by the intraperitoneal route.

Based on the previous demonstration of a high peritoneal-to-plasma ratio of drug exposure for intraperitoneal (IP) etoposide, the authors performed a clinical/pharmacokinetic trial of etoposide (600 mg/m2) in combination with cisplatin (100 mg/m2). The drugs were administered concurrently IP, and allowed to dwell for 4 hours, after which the peritoneum was drained. Six patients received 13 cycles of treatment. Grade 4 neutropenia occurred in three patients; toxicity was otherwise moderate. Plasma etoposide concentrations reached a peak at 4.2 +/- 2.5 hours and declined exponentially with a terminal half-life of 9.5 +/- 3.6 hours. Peritoneal etoposide concentrations declined monoexponentially with a half-life of 3.7 +/- 2.6 hour. The calculated peritoneal-to-plasma ratio of unbound etoposide was 35. The plasma and peritoneal half-lives of ultrafilterable cisplatin were 21.7 +/- 14.1 hours and 1.8 +/- 0.7 hours, respectively. The peritoneal/plasma area under curve AUC ratio was 18.3. These pharmacokinetic indices for both drugs are consistent with those obtained with the use of each drug as a single agent. Thus, the concomitant use of one does not alter the pharmacokinetic activity of the other. The high AUC ratios support the further clinical development of these drugs in combination in the intraperitoneal setting.

Adenocarcinoma↗
PubMed1991

Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer.

Amonafide, a benzisoquinoline-1,3-dione with anti-tumor activity in preclinical screens, was administered to patients with recurrent or metastatic bidimensionally measurable colorectal cancer. Fourteen patients with no prior chemotherapy for advanced disease, performance status 0-1, and normal bone marrow, renal, and hepatic function were entered. Amonafide 300 mg/m2 was administered intravenously over 1 hour daily for five consecutive days; courses were repeated every three weeks. The major side effect was neutropenia: Grade 3 or 4 toxicity occurred in 5/14 patients. Other toxicities included nausea and vomiting, flulike symptoms, fever, rash and alopecia. Three patients had stable disease, but there were no responses observed. Amonafide at this dose and schedule has no activity in the treatment of colorectal cancer.

Adenine↗
PubMed1991

Phase II trial of thio-TEPA in relapsed and refractory ovarian carcinoma.

On the basis of a Phase I reevaluation of thio-TEPA in which 3 of 9 patients with ovarian carcinoma responded, we instituted a Phase II study at high doses. Fourteen patients with a histologic diagnosis of epithelial carcinoma of the ovary, who had received at least one prior cisplatin-based regimen, were entered. Thio-TEPA was initially administered intravenously at a dose of 65 mg/m2 every 4 weeks, but was reduced to 50 mg/m2 after severe myelotoxicity developed in the first 5 patients. In 4 patients stable disease lasted 3, 4, 5, and 9 months; 10 patients progressed. There were no objective responses. At this dose and schedule, thio-TEPA has a response rate less than 20% in ovarian cancer patients previously treated with cisplatin.

Adenocarcinoma↗
PubMed1991

Phase II study of weekly 5-fluorouracil, cisplatin and vinblastine in advanced non-small cell lung cancer.

The scheduling of chemotherapeutic agents may be important in optimising their antitumour actions. This has been explored in non-Hodgkin lymphoma, osteogenic sarcoma and bladder cancer with improved results using intensive, weekly dosing schemas. We began a phase II study of cisplatin, 5-fluorouracil and vinblastine in non-small cell lung cancer (NSCLC) on a weekly schedule. 38 patients with advanced or metastatic NSCLC were entered; 32 are evaluable for response. 11 patients were treated with 5-fluorouracil 1.5 g/m2 and vinblastine 4 mg/m2 by 24-h continuous infusion, and cisplatin 30 mg/m2 over 30 min, 6-8 h after the start of the infusion. Because of prohibitive myelotoxicity, the next 27 patients received 5-fluorouracil 1.2 g/m2 and vinblastine 3 mg/m2. None had had prior chemotherapy while 6 had had previous radiation therapy. Myelosuppression was the predominant toxic effect. Other side-effects included neuropathy, diarrhoea, mucositis, nausea and vomiting. 32 patients are evaluable for response: there have been 14 partial remissions (44%). Responses have occurred chiefly in lung and lymph nodes. The median survival on this study is 7 months, and responders did not live longer than non-responders. While this regimen is well tolerated by the majority of patients and has a response rate comparable to other active regimens identified in single institution studies, survival does not appear to be enhanced. We conclude that the schedule manipulation described here does not enhance the therapeutic index of these drugs in NSCLC.

Adult↗
PubMed1991

Etoposide and mitomycin in the treatment of non-small-cell lung cancer. A phase I-II evaluation.

Sixty-five patients (20 patients who had had prior radiotherapy and 45 patients who had not had prior radiotherapy) were entered into a study evaluating escalating doses of etoposide and mitomycin in the treatment of non-small-cell lung cancer (NSCLC). Twenty-two percent of patients who had not received prior radiotherapy responded to the chemotherapy, compared with 5% of patients who had received prior radiotherapy. The best response rate and median survival time was 30% and 31.9 weeks, respectively, seen in three of 10 patients receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3. The major toxicity was hematologic--mainly leukopenia, in 59% of patients who had had no prior radiation therapy and were receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 150 mg/M2 i.v. days 1-3 (grade 3 and 4 hematologic toxicity). The mitomycin-etoposide drug combination has some activity in patients with NSCLC who have not received prior radiotherapy. The recommended starting dose is mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3, administered every 4 weeks.

Adenocarcinoma↗
PubMed1991

Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease.

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.

Adult↗
PubMed1991

Socioeconomic status and cancer survival.

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.

Adolescent↗
PubMed1990

Phase II trial of etoposide and cisplatin for refractory small cell lung cancer: a Cancer and Leukemia Group B Study.

A phase II trial of etoposide and cisplatin for patients with previously treated small cell lung cancer was carried out by CALGB from June 1983 to May 1984. Thirty-five evaluable patients who had failed one prior chemotherapy regimen were treated with etoposide 80 mg/m2 and cisplatin 20 mg/m2 days 1-5 every 3 weeks. Objective responses were seen in 7 patients (20%) with 1 complete response and 6 partial responses. The median duration of response was 5.1 months. Fifteen patients (43%) had stable disease. Overall survival was 49% at 6 months and 14% at 1 year. The median survival was 6 months. Toxicity was mainly hematologic with severe and life-threatening leukopenia and thrombocytopenia seen in 71% and 66% of patients, respectively. Two treatment-related deaths caused by infection were seen. This cooperative group study fails to confirm the high response rates previously reported in institutional pilot studies.

Adult↗
PubMed1990

Phase I trial of tallysomycin S10b, a bleomycin analogue.

Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose- or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 beta half-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma, rectal cancer and lung cancer. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma.

Adult↗
PubMed1990

Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas.

Ninety-eight patients with previously-treated advanced soft tissue sarcoma, bone sarcoma, or mesothelioma were randomly assigned to one of two intravenous single-agent treatment regimens, either 6-diazo-5-oxo-l-norleucine (DON; brief infusions of 50 mg/m2/day for 5 consecutive days every 4 weeks) or aclacinomycin-A (ACM-A, as 30-min infusions of 100 mg/m2 or 85 mg/m2, administered every 3 weeks). Of 43 patients who were evaluable for response, survival and toxicity, there were two responses (5%) produced by ACM-A; one in a male with mesothelioma, and one in a female with malignant fibrous histiocytoma. None of the 36 evaluable patients treated with DON developed an objective tumor response. Median survival was 4.8 months in the DON treatment arm, and 6.8 months in the ACM-A treatment arm. No patients on the DON arm experienced lethal or life-threatening toxicities, and severe toxicities resulting from this treatment included nausea and emesis (10%), stomatitis (2%), gastrointestinal toxicity (2%), and anemia (2%). Moderate toxicities included vomiting (24%), hematologic toxicity (24%), neurologic toxicity (7%), diarrhea (7%), mucositis (5%), fever (5%), palpitations (2%), hepatotoxicity (2%), bleeding (2%) and edema (2%). Fifteen percent experienced at least one severe reaction, and 63% experienced at least one moderate or greater toxicity. ACM-A was associated with four cases of life-threatening myelosuppression (7%); severe toxicities included myelosuppression (11%), neurologic toxicity (4%), diarrhea (2%), respiratory toxicity (2%), pain and muscle spasms (2%), edema (2%), and ulceration following extravasation (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aclarubicin↗
PubMed1990

Phase I trial of 5-fluorouracil, leucovorin, and cisplatin in combination.

The ongoing evaluation of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in several tumors prompted a phase I clinical trial of cisplatin with 5-FU modulated by leucovorin. A total of 26 patients were treated with varying doses of 5-FU by continuous i.v. infusion for 5 days; 200 mg/m2 leucovorin was given by daily bolus injection for 5 days; and 20 mg/m2 cisplatin was infused over 2 h on each day of treatment. Courses were repeated every 21-28 days. The starting dose of 5-FU was 300 mg/m2. Poor-risk patients (extensive prior radiation, performance status of 2 or worse) did not tolerate the initial dose; the maximum tolerated dose of 5-FU in this group was 200 mg/m2 daily. Good-risk patients tolerated 300 mg/m2, but a majority had excessive toxicity at higher doses. The dose-limiting toxicity was gastrointestinal (mucositis/diarrhea) and/or myelosuppression; additional side effects included were nausea and vomiting (less than or equal to grade 2) and ataxia (one patient). Among 13 patients with colorectal cancer, 4 partial responses were observed. The marked reduction in the tolerable dose of 5-FU occasioned by the addition of modulating doses of leucovorin is noteworthy. The responses observed support further investigation of this regimen in phase II trials.

Aged↗
PubMed1990

Assignment of 35 single-copy and 17 repetitive sequence DNA probes to human chromosome 3: high-resolution physical mapping of 7 DNA probes by in situ hybridization.

Thirty-five single-copy and 17 repetitive sequence DNA probes specific for human chromosome 3 were isolated from human chromosome 3-derived genomic libraries. Seven DNA clones, including three that are polymorphic for BglII or MspI, were mapped by in situ hybridization. Four probes were mapped to 3p subregions and 3 were mapped to 3q subregions. Three of the DNA sequences map to regions overlapping a segment of chromosome 3 (3p14-23) frequently deleted in small cell lung cancer cells. By Southern blot analysis on a deletion hybrid panel, we previously mapped 6 of these probes to three distinct chromosome 3 subregions. Our in situ data support these assignments and more precisely determine the localization of each clone to the following regions: D3S34 (3p14-21), D3S35 (3p21), D3S39 (3p21), D3S40 (3p12-13), D3S37 (3q21-23), and D3S36 (3q21). Clone pL84c, a low repeat sequence clone (approximately 30 copies), was mapped to the 3q21-29 subregion. These DNA clones mapped by in situ hybridization can provide useful landmarks for the ordering and localization of other clones.

Chromosome Mapping↗
PubMed1990

Phase II trial of carboplatin in soft-tissue sarcoma.

As part of the Eastern Cooperative Oncology Group program for the assessment of new drugs in sarcomas, a Phase II trial of carboplatin was performed in patients who had received no more than one prior chemotherapy regimen. A total of 50 patients received either 400 mg/m2 or 320 mg/m2 depending on whether they had received prior radiotherapy. A response rate of 16% (95% confidence interval 6-32%) occurred in the 37 patients who had received doxorubicin as their only prior systemic therapy. Three of the six responses were complete and persisted for 7 to 34 months. In contrast none of the 13 patients who received carboplatin after initial progression on doxorubicin and subsequent progression on interferon alpha responded. The overall response rate was therefore 12% (95% confidence interval 5-24%). Toxicity was primarily hematologic, with 14 patients having Eastern Cooperative Oncology Group (ECOG) grade 3 toxicity and no grade 4 or 5 toxicities. In view of the number of complete responses, carboplatin should be studied further in untreated patients with advanced soft tissue sarcoma.

Adult↗
PubMed1990

Renal cell carcinoma: treatment with recombinant interleukin-2 plus beta-interferon.

Preclinical data have demonstrated synergy between interleukin-2 (IL-2) and beta-interferon (IFN-beta) in stimulating natural-killer (NK) cell activity and in increasing expression of IL-2 receptors. Based on results of a phase I trial, a combination of IL-2 and IFN-beta was administered three times weekly by intravenous (IV) bolus injection with 5 x 10(6) Cetus U/m2 of IL-2 and 6 x 10(6) U/m2 of IFN-beta to 24 patients with advanced renal cell carcinoma (RCC). Of 22 assessable patients there were six (27%) objective responses including one complete remission (CR) and five partial responses (PRs). There were three minor responses (MRs), 11 stable disease (SD), and two progressive disease (PD). Two of the objective responses have continued for almost 2 years. Response sites include lymph nodes, lungs, and bone. Toxicities requiring dose reduction include arthralgia, weight loss, fatigue, decreased performance status, depression, and hypotension. Five of 10 patients who had a prior nephrectomy without local recurrence achieved an objective response as compared with only one of 12 without a prior nephrectomy or with a local recurrence (P = .04). Mean peak lymphokine-activated killer (LAK) cell activity of the objective responders was 88 lytic units (LU) as compared with 4 LU in the nonresponders (P = .01). Mean peak NK cell activity was 288 LU in the objective responders as compared with 100 LU in the nonresponders (P = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Phase II study of biochemical modulation of fluorouracil by low-dose PALA in patients with colorectal cancer.

Higher response rates in colorectal cancer have been observed with regimens that increase the cytotoxicity of fluorouracil (5-FU) by altering the biochemical milieu at its site(s) of action. Phosphonacetyl-L-aspartate (PALA), which inhibits aspartate transcarbamylase and depletes uridine nucleotide pools in vitro and in vivo, selectively potentiates the antitumor activity of 5-FU in preclinical models. In a phase I/II study in patients with advanced colorectal cancer, PALA 250 mg/m2 was given on day 1, followed 24 hours later by 5-FU 2,600 mg/m2 by 24-hour infusion repeated weekly. Through the use of subcutaneous ports and portable infusion pumps, all patients were treated outside the hospital setting. Thirty-nine patients without prior chemotherapy received 884 courses of treatment. The primary site was colon in 31, rectum in eight. Toxicity was generally mild to moderate except among four patients who were escalated to 5-FU 3,250 mg/m2: two developed severe gastrointestinal toxicity and myelosuppression. Among the remaining 35 patients, gastrointestinal and neurologic toxicities predominated, but usually did not develop until the third or fourth month of treatment. Two patients were inevaluable for response. Among the 37 evaluable patients there were three complete and 13 partial remissions for a total response rate of 43% (95% confidence interval [Cl], 27% to 59%). The median duration of response was 5 months (range, 1.5 to 15 months). The projected mean survival is in excess of 17 months. This high response rate is comparable to the best results obtained with other means of modulation of 5-FU. Demonstration of a survival benefit will require larger phase III studies.

Adenocarcinoma↗
PubMed1989

A phase II study of mitoguazone and vinblastine in advanced transitional cell carcinoma of the urinary tract.

This is a comparative study to evaluate response rate to mitoguazone (MGBG) and vinblastine (VLB) in 52 evaluable patients with advanced transitional cell carcinoma of the urinary tract. Of 38 patients with measurable disease, two of 18 (11%) on MGBG had partial remission (95% confidence interval: 0.01, 0.35), whereas four of 20 (20%) responded on the VLB arm (95% confidence level: 0.06-0.44). Both responses on the MGBG arm were seen in patients given prior chemotherapy. Side effects of both drugs were significant, with 46% of patients given VLB developing severe or life-threatening hematologic toxicity. Data indicate that both drugs, as single agents, are probably inferior to cisplatin for control of advanced transitional cell carcinoma of the urinary tract.

Carcinoma, Transitional Cell↗