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Biomedical subjects

C D Kowal

Publications and source records attributed to C D Kowal.

12 recordsLinked to original sources
PubMed1997

Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion.

PURPOSE: To compare the toxicity, pharmacokinetics, and efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (I.P.) interleukin-2 (IL-2) by two different infusion schedules. PATIENTS AND METHODS: Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m2/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy. Eligibility criteria included > or = six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer. RESULTS: Forty-one eligible patients received I.P. IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m2 as the maximum-tolerated dose (MTD), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established. Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35). The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%. For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months). CONCLUSION: I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.

Adult↗
PubMed1996

Lack of effect of corticosteroids and tamoxifen on suramin protein binding and in vitro activity.

Stout and colleagues [Proc Am Assoc Cancer Res 1993, 34, p. 298] previously reported that both hydrocortisone and tamoxifen increased the free fraction of suramin in human plasma. We examined several corticosteroids as well as tamoxifen for their effects on suramin protein binding and also evaluated hydrocortisone for its ability to modulate suramin activity in PC-3 and MCF-7 cells. Greater than 99% of the suramin was protein bound in undiluted human plasma. However, the free fraction of suramin was increased with the reduced plasma protein levels and increased suramin concentrations. At concentrations ranging from 1 to 30 microM, neither tamoxifen, hydrocortisone, prednisone nor dexamethasone had any effect on the binding of suramin to human plasma, regardless of protein concentrations. Similar results were observed with fetal calf serum. Hydrocortisone also had no effect on suramin activity against PC-3 and MCF-7 cell in vitro. We conclude from these studies that neither corticosteroids nor tamoxifen affect suramin protein binding or its cytotoxic activity.

Anti-Inflammatory Agents↗
PubMed1992

Characterization of oxyphenarsine as a potential antiviral agent for AIDS.

The historical antisyphilis drug oxyphenarsine has been tested for antiviral activity and for cytotoxicity to characterize it as a potential therapy for treatment of HIV infections. These data show that the compound demonstrates marginal antiviral activity against the HTLV-IIIB strain of HIV-1, two clinical isolates of HIV-1 (one sensitive to AZT and one resistant), and the MS strain of HIV-2. However, treatment with concentrations of oxyphenarsine showing optimal anti-HIV activity resulted in significant cytotoxicity. The drug's selectivity index was not significantly improved when tested against H9 cells chronically infected with the HTLV-IIIB strain of HIV-1. Thus, despite a previous report suggesting significant antiviral activity and low cytotoxicity for oxyphenarsine, the data presented here do not provide support for further development of this drug as an anti-HIV agent.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Nucleotide derivatives of 2,7-diaminomitosene.

Treatment of mitomycin C with pyrimidine nucleotides in acidic media produced derivatives of 2,7-diaminomitosene in which C-1 was covalently bound to the phosphate group of the nucleotides. On reduction, these derivatives liberated the nucleotides and a mitomycin intermediate that alkylated DNA. Their reduction in the presence of 2'-deoxyguanosine produced some bifunctional alkylation as did mitomycin C. They were readily taken up by L1210 leukemia cells, in which they showed potent cytotoxicity. These properties suggest that they are acting as prodrugs capable of conversion into two active species. The uridylate derivative showed activity comparable to that of mitomycin C against P-388 leukemia in mice.

Alkylation↗
PubMed1988

Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA.

Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

Antibodies, Monoclonal↗
PubMed1985

Brachial plexus myoclonus.

Rhythmic myoclonus in an arm began abruptly following an injury and persisted continuously for six years. Topographical EMG showed abnormal activity confined to muscles innervated by the axillary and radial nerves from the posterior cord of the brachial plexus. Abduction of the arm above horizontal level stopped myoclonus and EMG discharges. EEG was normal. It is suggested that the myoclonus was caused by mechanical irritation of the posterior cord of the brachial plexus.

Brachial Plexus↗
PubMed1983

Methotrexate and 5-fluorouracil in sequence in squamous head and neck cancer.

5-Fluorouracil (5-FU), when preceded by methotrexate (MTX), results in synergistic tumor cell kill both in vitro and in vivo in mice. Since MTX concentrations 10 microM or greater maximize the synergy in vitro, we administered sequential MTX-5-FU as follows: MTX 125-250 mg/m2 i.v. followed 1 hr later by 5-FU 600 mg/m2 i.v. Leucovorin (LV) rescue 10 mg/m2 i.v. was given at hr 24, then 10 mg/m2 p.o. every 6 hr for 5 doses. One-hour and 24-hr serum MTX levels were monitored and 24-hr serum creatinine levels obtained. A weekly schedule was adhered to where possible, although most patients had at least one course delayed during the first month of treatment because of toxicity. Maintenance was every 2 wk. Since our initial report (Proc Am Soc Clin Oncol 21:473, 1980), a total of 35 squamous cell head and neck cancer patients, 12 with de novo and 23 with recurrent or metastatic disease, have been treated. Overall response rate is 71%, 65% in recurrent patients, 83% in de novo patients. Complete response rate was 11%. Median response duration for recurrent patients was 3.6 mo. With all deaths scored as disease-related and a minimum follow-up of 18 mo in all patients, a median survival of 11.5 mo for the 23 recurrent and 12 mo for the de novo patients was seen. Pretreatment performance status affected survival with Eastern Cooperative Oncology Group (ECOG) 0-1 patients living significantly longer than bedridden patients (p less than 0.001). Toxicity was either hematologic or gastrointestinal, with diarrhea, the limiting toxicity, accounting for the one drug-related death. The MTX/5-FU combination sequence may provide significant long-lasting palliation in patients with recurrent squamous head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1981

Enhancement by hyperthermia of the in vitro cytotoxicity of mitomycin C toward hypoxic tumor cells.

Mitomycin C and hyperthermia are both toxic to chronically hypoxic EMT6 tumor cells. Combinations of this drug and heat were tested in vitro in normally aerated and chronically hypoxic EMT6 mouse mammary tumor cells to establish whether greater than additive cytotoxicity could be achieved by combined treatment. Cell survival was measured at four concentrations of mitomycin C (0.01, 0.1, 1.0, and 10 microM) at 37 degrees or at elevated temperatures (41, 42, and 43 degrees) for durations of 1, 2, 3, and 6 hr. At 42 degrees, exposure to mitomycin C for 3 and 6 hr produced a 2- to 3-fold increase in hypoxic tumor cell kill at all drug concentrations over that expected for strict additivity. A 15-fold enhancement in the kill of hypoxic tumor cells was obtained at 1.0 and 10 microM mitomycin C at 43 degrees for 6 hr of exposure. Under most conditions, additivity was observed for the antibiotic and heat in oxygenated cells, except at 43 degrees with 0.01 and 0.1 microM mitomycin C following 3 and 6 hr of treatment, conditions under which a 5- to 10-fold potentiation of tumor cell kill was obtained. The rate of formation of reactive metabolites from mitomycin C under anaerobic conditions in EMT6 cell-free preparations was measured. A 30 to 50% increase in alkylating activity was observed at elevated temperatures, suggesting that the enhanced cytotoxicity of mitomycin C with heat toward hypoxic cells may, in part, be due to an increase in activation of the drug.

Aerobiosis↗
PubMed1979

Possible benefits of hyperthermia to chemotherapy.

The advantages of hyperthermia for chemotherapy are discussed in detail. These advantages are (a) synergy with chemotherapeutic drugs and also with ionizing radiation, (b) low host toxicity, (c) ease of control (heating precisions in the range of +/- 0.1 degrees C and specific definable localized areas), and (d) low resistance (chemotherapeutic resistance and hyperthermic resistance). The potential for hyperthermia and chemotherapy in the treatment of specific human cancers, both disseminated and solid tumors, are discussed with respect to current therapy and the possible benefit of hyperthermia treatment.

Antineoplastic Agents↗