Compounds > 1h-pyrrole-2-5-dione--3-(1-methyl-1h-indol-3-yl)-4-(1-methyl-6-nitro-1h-indol-3-yl)-

1h-pyrrole-2-5-dione--3-(1-methyl-1h-indol-3-yl)-4-(1-methyl-6-nitro-1h-indol-3-yl)- and Carcinoma

1h-pyrrole-2-5-dione--3-(1-methyl-1h-indol-3-yl)-4-(1-methyl-6-nitro-1h-indol-3-yl)- has been researched along with Carcinoma* in 1 studies

Trials

1 trial(s) available for 1h-pyrrole-2-5-dione--3-(1-methyl-1h-indol-3-yl)-4-(1-methyl-6-nitro-1h-indol-3-yl)- and Carcinoma

Article	Year
A phase I clinical and pharmacokinetic study of Ro 31-7453 given as a 7- or 14-day oral twice daily schedule every 4 weeks in patients with solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Jul-01, Volume: 10, Issue:13 This is a dose-finding Phase I study of oral Ro 31-7453, a new class of antimitotic drug with promising preclinical activity in several chemoresistant models.. Two schedules of oral Ro 31-7453 (every 12 h) given for either 7 or 14 consecutive days repeated every 4 weeks were explored consecutively.. Thirty-seven patients with refractory cancer entered the study (14 on the 7-day schedule and 23 on the 14-day schedule). Median age was 63 years (range, 40-77 years), and median Karnofsky performance status was 80 (range, 60-100); the most frequent diagnosis was colorectal carcinoma (16 patients). Dose levels of 100, 200, 240, and 280 mg/m(2) twice daily (bid) for 7 days and 70, 100, 125, and 150 mg/m(2) bid for 14 days were explored. A total of 110 cycles were administered, the median number of cycles received was 3 (range, 1-7); six patients completed 6 or more cycles. Myelosuppression and mucositis were dose-limiting with both schedules. Fatigue and gastrointestinal toxicities other than mucositis were frequent but generally mild. The maximum tolerated doses were 200 mg/m(2) bid and 125 mg/m(2) bid for the 7- and 14-day schedules, respectively. Pharmacokinetic analysis showed rapid absorption and metabolism. The area under the concentration-time curve and trough concentrations of Ro 31-7453 and two active metabolites appeared dose proportional with a t(1/2) of approximately 9 h and a t(max) of approximately 4 h. One patient with pretreated lung cancer had a partial response.. Both Ro 31-7453 regimens were feasible, but the 14-day schedule at the recommended dose of 125 mg/m(2) bid was selected for further monotherapy Phase II evaluation because of its higher preclinical activity. This regimen is convenient, well tolerated, and has a favorable pharmacokinetic profile. Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Carcinoma; Colorectal Neoplasms; Dose-Response Relationship, Drug; Edetic Acid; Female; Humans; Indoles; Male; Middle Aged; Models, Chemical; Neoplasms; Time Factors	2004

Article

Year

A phase I clinical and pharmacokinetic study of Ro 31-7453 given as a 7- or 14-day oral twice daily schedule every 4 weeks in patients with solid tumors.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Jul-01, Volume: 10, Issue:13

This is a dose-finding Phase I study of oral Ro 31-7453, a new class of antimitotic drug with promising preclinical activity in several chemoresistant models.. Two schedules of oral Ro 31-7453 (every 12 h) given for either 7 or 14 consecutive days repeated every 4 weeks were explored consecutively.. Thirty-seven patients with refractory cancer entered the study (14 on the 7-day schedule and 23 on the 14-day schedule). Median age was 63 years (range, 40-77 years), and median Karnofsky performance status was 80 (range, 60-100); the most frequent diagnosis was colorectal carcinoma (16 patients). Dose levels of 100, 200, 240, and 280 mg/m(2) twice daily (bid) for 7 days and 70, 100, 125, and 150 mg/m(2) bid for 14 days were explored. A total of 110 cycles were administered, the median number of cycles received was 3 (range, 1-7); six patients completed 6 or more cycles. Myelosuppression and mucositis were dose-limiting with both schedules. Fatigue and gastrointestinal toxicities other than mucositis were frequent but generally mild. The maximum tolerated doses were 200 mg/m(2) bid and 125 mg/m(2) bid for the 7- and 14-day schedules, respectively. Pharmacokinetic analysis showed rapid absorption and metabolism. The area under the concentration-time curve and trough concentrations of Ro 31-7453 and two active metabolites appeared dose proportional with a t(1/2) of approximately 9 h and a t(max) of approximately 4 h. One patient with pretreated lung cancer had a partial response.. Both Ro 31-7453 regimens were feasible, but the 14-day schedule at the recommended dose of 125 mg/m(2) bid was selected for further monotherapy Phase II evaluation because of its higher preclinical activity. This regimen is convenient, well tolerated, and has a favorable pharmacokinetic profile.

Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Carcinoma; Colorectal Neoplasms; Dose-Response Relationship, Drug; Edetic Acid; Female; Humans; Indoles; Male; Middle Aged; Models, Chemical; Neoplasms; Time Factors

2004