Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer

Murren, John R.; Peccerillo, Kathleen; DiStasio, Susan A.; Li, Xin; Leffert, Janine J.; Pizzorno, Giuseppe; Burtness, Barbara; McKeon, Anne; Cheng, Yung Chi

doi:10.1007/s002800000115

Cited by 18 publications

(10 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This less thrombocytopenic regimen may also be helpful in the treatment of elderly patients. A phase I study of Pac and CPT combination chemotherapy showed that neutropenia was dose-limiting, and Pac 75 mg/m 2 and CPT 50 mg/m 2 were recommended [27]. The difference in the recommended dose between that study and ours can be attributed to the fact that we used prophylactic G-CSF when monocytopenia developed after the start of chemotherapy.…”

Section: Discussionmentioning

confidence: 81%

Dose Escalation Study of Paclitaxel in Combination with Fixed-Dose Irinotecan in Patients with Advanced Non-Small Cell Lung Cancer (JCOG 9807)

Yamada¹,

Ikehara²,

Tanaka³

et al. 2004

Oncology

View full text Add to dashboard Cite

Background: Both irinotecan (CPT) and paclitaxel (Pac) are effective against non-small cell lung cancer (NSCLC), and besides, preclinical studies have demonstrated an additive or synergistic interaction between camptothecin and taxane. Methods: We conducted a phase I/II study of combination chemotherapy consisting of Pac and CPT to determine qualitative and quantitative toxicities and efficacy of the combination against advanced NSCLC. We fixed the dose of CPT at 60 mg/m² and escalated the Pac dose in 10 or 20 mg/m² increments from a starting dose of 80 mg/m², and repeated the cycle every 2 weeks. Prophylactic G-CSF was also administered. Results: Between February 1999 and April 2001, 24 patients were registered in the study. None of the patients had a history of prior chemotherapy, but surgical resection had been performed in 3 of them. None of the patients experienced dose-limiting toxicity (DLT) up to and including level 6. At dose level 7 of Pac, 180 mg/m², 2 patients experienced DLT, that is grades 2 and 3 dyspnea due to pneumonitis. Another patient experienced grade 1 dyspnea due to pneumonitis. Neutropenia, diarrhea, and other toxicities were mild; however, we concluded that dose level 7 of Pac was the maximum-tolerated dose. An objective response was observed in 58.3%. The median survival time was 370 days, and the 1-year survival rate was 54.2%. Conclusion: Pneumonitis was the DLT in this study, and Pac 160 mg/m² and CPT 60 mg/m² every 2 weeks are recommended for the phase II study. This combination shows appreciable activity against NSCLC.

show abstract

Section: Discussionmentioning

confidence: 81%

Dose Escalation Study of Paclitaxel in Combination with Fixed-Dose Irinotecan in Patients with Advanced Non-Small Cell Lung Cancer (JCOG 9807)

Yamada¹,

Ikehara²,

Tanaka³

et al. 2004

Oncology

View full text Add to dashboard Cite

show abstract

“…On the other hand, Murren et al . conducted a dose escalation study for advanced cancers and RDs of weekly paclitaxel at 75 mg/m 2 and weekly irinotecan at 50 mg/m 2 18 . Rushing et al .…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, Murren et al conducted a dose escalation study for advanced cancers and RDs of weekly paclitaxel at 75 mg/m 2 and weekly irinotecan at 50 mg/m 2 . 18 Rushing et al also conducted Phase I/ II studies for advanced small cell lung cancer and RDs of weekly paclitaxel at 50 mg/m 2 and weekly irinotecan at 60 mg/m 2 , at which the efficacy rate was 75%. 19 Based on the above findings, we investigated the dose level and safety of combined therapy with irinotecan and paclitaxel by weekly administration in a Phase I study, followed by clinical effects in a Phase II study.…”

Section: Discussionmentioning

confidence: 99%

Phase I study of paclitaxel plus irinotecan combination therapy for patients with refractory and advanced gastric cancer

Kobayashi

Sakagami

Koizuka

et al. 2006

Ali Pharm Thera Symp Ser

View full text Add to dashboard Cite

Summary Background No adequate second‐line chemotherapy regimen for advanced gastric cancer is available. Aims To determine the safety and optimal dose of paclitaxel/irinotecan as a second‐line chemotherapy for patients with advanced and recurrent gastric cancer. Patients and methods Sixteen patients with refractory and advanced measurable gastric cancer who were resistant to 5‐FU plus cis‐diamminedichloroplatinum (CDDP) therapy (FP) were enrolled. Paclitaxel/irinotecan was given intravenously on days 1, 8, and 15 in repeated 4‐week cycles. Paclitaxel/irinotecan doses were escalated in a stepwise fashion as follows: 50/40 mg/m2, 50/50 mg/m2, 50/60 mg/m2, 60/60 mg/m2, 60/70 mg/m2 in levels I, II, III, IV and V, respectively. Results Because of one patient with Grade 3 febrile neutropenia at level I, three more patients were enrolled in level I. Doses were consequently escalated, and in level IV, Grade 3 febrile neutropenia occurred in one patient. Since an additional patient in level IV had grade 4 neutropenia, Level IV was judged as the maximum tolerated dose (MTD). The recommended dose and schedule for phase II study is paclitaxel 50 mg/m2 and irinotecan 60 mg/m2 on days 1, 8, and 15 every 4 weeks. Partial response was observed in 4 of 16 patients. Conclusion Paclitaxel/irinotecan combination regimen at the level III dosage was safe and well tolerated.

show abstract

“…Rosen et al also reported that dose escalation of the two drugs above the starting dose (irinotecan 225 mg/m 2 and paxlitaxel 100 mg/m 2 , once every 3 weeks) was impossible because of neutropenic fever or severe diarrhea [14]. On the other hand, Murren et al investigated the combination of the two drugs in a weekly schedule for patients with advanced various cancers, and concluded that this combination was well tolerated, although they experienced several adverse events in the patients treated with the recommended dose [15]. These results suggest that the combination of irinotecan and paclitaxel produces relatively severe toxicities, compared with other regimens containing irinotecan or paclitaxel such as cisplatin plus irinotecan or carboplatin plus paclitaxel [5,16].…”

Section: Discussionmentioning

confidence: 99%

A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer

et al. 2004

View full text Add to dashboard Cite

show abstract

Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer

Abstract: The recommended dose of irinotecan on this schedule is 50 mg/m2. The sequence of drug administration affects neither the elimination of irinotecan nor the chemotherapy-related toxicity. This combination is well tolerated and causes minimal clinical side effects.

Cited by 18 publications

References 20 publications

Dose Escalation Study of Paclitaxel in Combination with Fixed-Dose Irinotecan in Patients with Advanced Non-Small Cell Lung Cancer (JCOG 9807)

Dose Escalation Study of Paclitaxel in Combination with Fixed-Dose Irinotecan in Patients with Advanced Non-Small Cell Lung Cancer (JCOG 9807)

Phase I study of paclitaxel plus irinotecan combination therapy for patients with refractory and advanced gastric cancer

A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer

Contact Info

Product

Resources

About