Abstract | BACKGROUND: To investigate the combination of S-1 and irinotecan (CPT-11) as an alternative to infusional 5-fluorouracil/ leucovorin plus CPT-11, we performed a phase I trial to determine the maximum tolerated dose, recommended dose (RD), and dose-limiting toxicities (DLTs) in patients with metastatic or recurrent colorectal cancer. PATIENTS AND METHODS: S-1 and CPT-11 doses were escalated using a standard 3 + 3 design. S-1 was administered orally at 70 mg/m(2) (levels 1-3) or 80 mg/m(2) (levels 4 and 5) for 14 consecutive days followed by 1-week rest. CPT-11 was administered intravenously on day 1, at 175 mg/m(2) (level 1), 200 mg/m(2) (level 2), 225 mg/m(2) (levels 3 and 4), or 250 mg/m(2) (level 5). Treatment was repeated every 3 weeks, unless disease progression or severe toxicities were observed. RESULTS: Twenty-three patients were treated. One patient at each of levels 2 and 4 developed a DLT, grade 3 ileus, and grade 3 diarrhea, respectively. At both levels, an additional three patients did not experience DLTs. At level 5, two of five patients experienced DLTs, including grade 3 enteritis and grade 4 neutropenia for more than 5 days. The RD was determined at level 4 (80 mg/m(2) S-1 and 225 mg/m(2) CPT-11). An objective response was observed in 7 of 17 patients with measurable disease: 2 of 5 at level 2; 3 of 4 at level 4; and 2 of 4 at level 5. CONCLUSIONS: The RDs of CPT-11 and S-1 were determined as 225 and 80 mg/m(2), respectively, and further phase II trials are warranted.
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Authors | Yoon Hee Choi, Tae Won Kim, Sung Sook Lee, Yong Sang Hong, Min-Hee Ryu, Jae-Lyun Lee, Heung Moon Chang, Yoon-Koo Kang |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 68
Issue 4
Pg. 905-12
(Oct 2011)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 21290246
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drug Combinations
- S 1 (combination)
- Tegafur
- Oxonic Acid
- Irinotecan
- Camptothecin
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects, therapeutic use)
- Camptothecin
(administration & dosage, analogs & derivatives)
- Colorectal Neoplasms
(drug therapy, pathology)
- Dose-Response Relationship, Drug
- Drug Combinations
- Female
- Humans
- Irinotecan
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasm Metastasis
- Neoplasm Recurrence, Local
- Oxonic Acid
(administration & dosage)
- Tegafur
(administration & dosage)
- Treatment Outcome
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