Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: a phase I study of the Arbeits gemeinschaft Internistische Onkologie (AIO).

TY - JOUR

T1 - Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: a phase I study of the Arbeits gemeinschaft Internistische Onkologie (AIO).

AU - Hartmann, Jorg Thomas

AU - Pintoffl, Jan Peter

AU - Kröning, Hendrik

AU - Bokemeyer, Carsten

AU - Holtmann, Martin

AU - Höhler, Thomas

PY - 2008

Y1 - 2008

N2 - BACKGROUND: The aim of the study was to establish the recommended dose and to evaluate the safety of gefitinib plus FUFOX regimen in irinotecan-refractory colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients with advanced CRC progressing on fluoropyrimidine/irinotecan-based chemotherapy and with an ECOG performance level 0-2 were enrolled. Four dose levels with sequential dose escalation of oral gefitinib and FUFOX were tested. Each cycle consisted of 5 weeks with gefitinib given daily to weekly FUFOX x4 to be repeated at day 36. RESULTS: Eighteen patients were enrolled. No dose-limiting toxicity (DLT) was observed at the dose levels L1-L3. At L4 diarrhea was the major DLT requiring treatment interruption in 3 patients. Other grade 3/4 toxicities were observed with skin rash, paresthesia, anemia, and nausea/vomiting (n = 1 each). Grade 1/2 toxicities consisted of diarrhea (n = 9), mucositis (8), skin rash (10), paresthesia (10), nausea (7) as well as leukopenia (2) and fever (1). Clinical benefit was seen in 11 of 16 evaluable patients (69%): 4 patients showed partial response (25%), 7 stable disease (44%). Median time to progression was 219 days (range 50-387 days). CONCLUSION: Gefitinib at a dose of 250 mg daily in combination with weekly 5-fluorouracil at 2,000 mg/m(2) or gefitinib at a dose of 500 mg daily with 5-fluorouracil at 1,600 mg/m(2) plus oxaliplatin has an acceptable safety profile.

AB - BACKGROUND: The aim of the study was to establish the recommended dose and to evaluate the safety of gefitinib plus FUFOX regimen in irinotecan-refractory colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients with advanced CRC progressing on fluoropyrimidine/irinotecan-based chemotherapy and with an ECOG performance level 0-2 were enrolled. Four dose levels with sequential dose escalation of oral gefitinib and FUFOX were tested. Each cycle consisted of 5 weeks with gefitinib given daily to weekly FUFOX x4 to be repeated at day 36. RESULTS: Eighteen patients were enrolled. No dose-limiting toxicity (DLT) was observed at the dose levels L1-L3. At L4 diarrhea was the major DLT requiring treatment interruption in 3 patients. Other grade 3/4 toxicities were observed with skin rash, paresthesia, anemia, and nausea/vomiting (n = 1 each). Grade 1/2 toxicities consisted of diarrhea (n = 9), mucositis (8), skin rash (10), paresthesia (10), nausea (7) as well as leukopenia (2) and fever (1). Clinical benefit was seen in 11 of 16 evaluable patients (69%): 4 patients showed partial response (25%), 7 stable disease (44%). Median time to progression was 219 days (range 50-387 days). CONCLUSION: Gefitinib at a dose of 250 mg daily in combination with weekly 5-fluorouracil at 2,000 mg/m(2) or gefitinib at a dose of 500 mg daily with 5-fluorouracil at 1,600 mg/m(2) plus oxaliplatin has an acceptable safety profile.

M3 - SCORING: Zeitschriftenaufsatz

VL - 31

SP - 237

EP - 241

JO - ONKOLOGIE

JF - ONKOLOGIE

SN - 0378-584X

IS - 5

M1 - 5

ER -