Biomedical subjects

Michael Tanaka

Publications and source records attributed to Michael Tanaka.

4 recordsLinked to original sources

PubMed2003

Phase I trial of gemcitabine and paclitaxel in advanced solid tumors.

PURPOSE: Gemcitabine and paclitaxel are chemotherapeutic agents with clinical antitumor activity in a broad range of malignant solid tumors. Because of preclinical synergy, unique mechanisms of action and resistance, and nonoverlapping toxicities, gemcitabine and paclitaxel combinations are attractive for testing in clinical trials. Prior weekly gemcitabine and paclitaxel regimens administered on a 28-day cycle have been limited by cumulative hematological toxicity on day 15, thus reducing the planned gemcitabine dose intensity. We therefore conducted a phase I trial of a 21-day schedule of weekly gemcitabine and paclitaxel to determine the tolerability, maximum tolerated dose (MTD), and preliminary estimates of efficacy of this regimen. PATIENTS AND METHODS: Forty-one patients with advanced malignant solid tumors were accrued. Gemcitabine was given at a fixed dose of 1000 mg/m2 while paclitaxel was administered at an initial dose of 60 mg/m2, then escalated by 15 mg/m2 increments over seven dose levels to a prospectively planned maximum dose of 150 mg/m2. Both agents were infused intravenously on days one and eight every 21 days. At least three patients were enrolled per dose level. No intrapatient dose escalation was allowed. RESULTS: All patients were assessable for toxicity and 31 were assessable for response. The regimen was generally well-tolerated. Dose-limiting thrombocytopenia was observed in one patient at a paclitaxel dose of 135 mg/m2/week (dose level 6). After expansion of this dose level by 14 additional patients, no further dose-limiting toxicities were observed although one patient at dose level seven died of neutropenic sepsis after completing three cycles. There were eight partial responders for an overall response proportion of 26% (95% CI: 11, 41). Twelve patients (39%) had stable disease. CONCLUSION: This 21-day schedule of gemcitabine and paclitaxel is safe, well-tolerated, and active. The recommended phase II dose is gemcitabine 1000 mg/m2 and paclitaxel 150 mg/m2 on days one and eight every 21 days. The antitumor activity observed with this regimen warrants further investigation.

Adult↗

PubMed2003

Population-based maximum tolerated dose of irinotecan and carboplatin.

A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics: men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.

Adult↗

PubMed2002

Premedication strategy for weekly paclitaxel.

PURPOSE: Dexamethasone and histamine antagonists have been employed commonly as premedications for prophylaxis of hypersensitivity reactions (HSRs) to paclitaxel. Frequent premedications for weekly administration of paclitaxel are associated with added side-effects and extra cost. We analyzed our experience of HSRs to paclitaxel administered every 3-4 weeks, and designed a treatment algorithm to eliminate premedications in a majority of patients receiving weekly paclitaxel. PATIENTS AND METHODS: The incidence of HSRs was analyzed retrospectively in patients who received 3-hr infusions of paclitaxel (135-225 mg/m2) every 3-4 weeks in our institution over a period of 5 years. On the basis of the results of this analysis, we designed a premedication schema for patients receiving weekly paclitaxel, 50-90 mg/m2/week, as follows: Thirty minutes prior to the first weekly dose of paclitaxel, patients received intravenously (i.v.) dexamethasone (10 mg), diphenhydramine (25 mg), and cimetidine (300 mg). If no HSRs occurred, all premedications were deleted for subsequent weekly paclitaxel doses. For patients who experienced HSRs, 20 mg of dexamethasone was given orally 12 and 6 hr prior to re-challenge with paclitaxel in addition to diphenhydramine and cimetidine. RESULTS: Over a period of 5 years, 358 patients received 1608 3-hr infusions of paclitaxel (135-225 mg/m2). Hypersensitivity reactions, which occurred exclusively during the first cycle of paclitaxel administration, were observed in 14 patients. Of these 14 patients, 11 were successfully retreated with paclitaxel without HSRs, two had recurrent HSRs upon paclitaxel re-challenge, and one refused further treatment. These observations indicate that HSRs to paclitaxel occurred in 4% of patients upon first exposure, that most of these patients can be retreated successfully with paclitaxel without recurrent HSRs, and that if no HSRs occur during the first cycle, HSRs are unlikely to occur with subsequent paclitaxel administration. The premedication schema was applied to 30 patients receiving 205 one-hr infusions of weekly paclitaxel. Using this premedication strategy, no HSRs have been observed during the initial or subsequent administration of paclitaxel. CONCLUSION: We conclude that this premedication strategy is feasible and worthy of further study for patients receiving weekly paclitaxel.

Administration, Oral↗

PubMedDate not supplied

An evaluation of barriers to accrual in the era of legislation requiring insurance coverage of cancer clinical trial costs in California.

PURPOSE: Clinical trials are essential to improve cancer therapy, but only 3% of newly diagnosed adult cancer patients enroll annually. We previously conducted a prospective analysis of factors affecting trial accrual at the UC Davis Cancer Center between 1997 and 2000. It was found that the accrual rate was 14% and that patients with private insurance were significantly less likely than patients with government insurance to enroll, suggesting that fear of insurance denial was a barrier. In 2002, a new California law (SB37) required insurers to reimburse routine costs of care for cancer trials. METHODS: To assess the impact of SB37 on accrual, we repeated our study using the same sur vey instrument. Oncologists seeing new patients at the UC Davis Cancer Center from August to November 2002 completed questionnaires that inquired about patient characteristics and eligibility, protocol availability, and patient willingness to participate. RESULTS: Physicians considered clinical trials for 55% (118/216) of patients, but trials were available for only 53% (62/118). Eligibility criteria were met by 82% (51/62). Of these, 69% (35/51) agreed to participate (vs 51% previously). No patient declined to participate because of insurance limitations (vs 8% previously). Furthermore, insurance type was no longer a significant factor in determining whether patients would enroll. This suggests that although the overall rate of accrual is only slightly increased after passage of SB37, patients may be more willing to enroll. Efforts to increase participation must include enhancing physician and patient awareness of SB37.

Adolescent↗