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Biomedical subjects

K M Pisters

Publications and source records attributed to K M Pisters.

42 records · Page 3Linked to original sources

Midazolam in patients receiving anticancer chemotherapy and antiemetics.

Benzodiazepines lessen anxiety and improve comfort in cancer patients. Midazolam is an effective benzodiazepine with a rapid onset and short duration of action, properties that could permit its use in outpatient areas or in short but stressful situations. Two consecutive trials were undertaken to study midazolam as an adjunct in patients receiving anticancer chemotherapy. Each studied midazolam given as a short infusion 30 min prior to chemotherapy at dose levels ranging from 0.01 to 0.05 mg/kg. Trial I determined the safety, sedation, and dose of midazolam in patients receiving chemotherapy of low to moderate emetic potential. Twenty-two patients were entered. No significant respiratory depression or oxygen desaturation was observed. At the optimal dose level (0.04 mg/kg), sedation began a median of 3 min following administration and continued for a median of 38 min. Sixty-four percent of patients experienced mild sedation. Trial II studied the same doses of midazolam when used in combination with intravenous metoclopramide and dexamethasone in patients receiving cisplatin > or = 100 mg/m2. Nineteen patients were entered; 79% experienced mild sedation. At the 0.04-mg/kg dose level, sedation began a median of 18 min following administration and continued for a median of 170 min. Midazolam can be given safely to patients receiving chemotherapy with and without concomitant antiemetics. The predictability and duration of its sedative effects suggest it can be used in outpatients.

Adult↗

Phase II trial of a single intravenous dose of ondansetron in patients receiving cisplatin > or = 100 mg/m2.

Ondansteron, a serotonin antagonist antiemetic, controls emesis caused by cisplatin when given as multiple 0.15 mg/kg dosages in a variety of administration schedules. This trial evaluated a single 0.45 mg/kg i.v. dose of ondansetron in 21 cancer patients receiving cisplatin at doses > or = 100 mg/m2 as initial chemotherapy. Twenty-five percent of patients had no emetic episodes (95% confidence interval: 9-49%), and 45% had two or fewer emetic episodes (95% confidence interval: 23-69%). No significant adverse effects were seen. In prior trials at this institution in similarly treated patients, ondansetron given in three divided doses yielded a 42% no emesis rate. In this trial a single i.v. 0.45 mg/kg dose of ondansetron prevented emesis in 25% of patients receiving initial cisplatin > or = 100 mg/m2. For this dose of cisplatin and ondansetron, the observed emesis complete control rate was lower than that previously seen using multiple dose schedules.

Adult↗

Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials.

PURPOSE: This report determines the incidence of pathologic complete response in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with mitomycin, vinca alkaloid, and high-dose cisplatin (MVP) chemotherapy, and estimates the effect of MVP on survival. PATIENTS AND METHODS: We have identified and reviewed the course of 21 patients with advanced NSCLC who achieved a pathologic complete response following a median of three preoperative MVP combination chemotherapy courses including vinblastine or vindesine, cisplatin (120 mg/m2), and mitomycin (n = 19). RESULTS: All patients had a major objective response following preoperative chemotherapy and nine (43%) had a clinical complete response. Nine patients with pathologic complete responses were among 73 entered on a preoperative chemotherapy program, yielding an incidence estimate of 12% (95% confidence interval, 6% to 22%). The median survival duration for all 21 patients has not been reached. The median follow-up duration is now 68 months (range, 17 to 109). Survival estimates are 90% at 1 year, 62% at 3 years, and 54% at 5 years. Nine patients have relapsed with initial sites of recurrence as follows: brain (n = 5), other systemic sites (n = 3), and locoregional (n = 1). One patient died in the postoperative period. Eleven patients remain disease-free and all have excellent functional status. CONCLUSION: We have observed pathologic complete responses in approximately 12% of advanced NSCLC patients treated with preoperative MVP chemotherapy. These pathologically determined responses were seen only in patients with major objective responses clinically. Pathologic complete response predicts excellent survival and functional level and should be considered a major end point in the evaluation of preoperative chemotherapy programs.

Adult↗

Management of nausea and vomiting caused by anticancer drugs: state of the art.

Our understanding and management of chemotherapy-induced nausea and vomiting has progressed substantially in the past decade. We now have many effective single agents, which are even more beneficial when used in appropriate combinations. A new class of antiemetic agents, the serotonin antagonists, of which ondansetron is the first to be commercially available, promises significantly better control of the various emetic syndromes caused by cancer chemotherapy, with fewer side effects. This article summarizes the state of the art of antiemetic therapy.

Antiemetics↗

Phase I study of paclitaxel administered by ten-day continuous infusion.

PURPOSE: Pre-clinical data have suggested that prolonged exposure to paclitaxel enhances its cytotoxicity, but various clinical trials utilizing long-term infusions of paclitaxel have been limited by unacceptable hematologic toxicity, most notably significant neutropenia. A phase I study of paclitaxel administered over 10 days, was performed to evaluate the hematologic and non-hematologic toxicities as well as to determine the maximum-tolerated dose for the 10-day infusion duration. PATIENTS AND METHODS: Twenty-nine solid tumor patients (predominantly non-small cell lung cancer and head and neck cancer) were treated with paclitaxel at doses ranging from 5 mg/m2/day to 25 mg/m2/day administered as a 10-day continuous infusion via a pump every 21 days. Dose escalation was permitted within individual patients. Dose-limiting toxicity (DLT) was defined as grade 3 or 4 non-hematologic toxicity, ANC < or = 500 or platelet count < or = 25,000 for > or = 7 days or febrile neutropenia. The maximum tolerated dose (MTD) was defined as the highest dose level at which less than two out of six patients developed DLT. All of the patients had received prior chemotherapy; approximately two-thirds had received prior radiation as well. All patients received standard pre-medications for paclitaxel, including anti-histamines and corticosteroids. Prophylactic granulocyte colony-stimulating factor (G-CSF) was not used. RESULTS: A total of 110 courses of paclitaxel were administered to 29 patients. The incidence of hematologic and non-hematologic toxicity was quite low among the patients treated at dose levels below 17 mg/m2/day. At higher doses, non-hematologic toxicities including arthralgias, myalgias, fatigue, nausea, stomatitis, and peripheral neuropathy were seen, although nearly all of the toxicities were less than grade 3 (NCI toxicity criteria). Hematologic toxicity mostly consisted of neutropenia and was more common at dose levels of 17 mg/m2/day or higher. Nevertheless, even at the highest dose levels (21 mg/m2/day and 25 mg/m2/day) grade 3 or 4 neutropenia occurred in only 50% of patients. Dose-limiting hematologic toxicity occurred in 2 of 4 patients treated at the 25 mg/m2/day dose level. CONCLUSION: Paclitaxel can be safely administered as a 10-day infusion. The MTD for this schedule is 210 mg/m2. Unlike the 96-hour paclitaxel infusions, dose-reduction for myelosuppression may not be necessary because the MTD of paclitaxel when administered over a 10-day infusion is similar to the MTD of paclitaxel when infused over 3 or 24 hours.

Adult↗