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Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 3735
© 2005 American Society of Clinical Oncology
Gemcitabine plus continuous infusion of 5-FU for heavily pretreated advanced colorectal cancer patients. Phase I/II study
V. Pachon,
P. Garcia-Alfonso,
L. Iglesias,
I. Siso,
G. Abad,
P. Khosravi,
V. Diaz and
G. Perez-Manga
Hosp Gregorio Marañón, Madrid, Spain
3735
Background: Colorectal cancer (CRC) patients previously treated with more than one regimen but still with good performance status are a frequent clinical reality. It is necessary to investigate effective therapies with low toxicity for them. Since gemcitabine (G) and 5FU are active drugs in this setting, we are performing a phase I/II trial in CRC multitreated patients with a bi-weekly schedule of G plus continuous infusion of 5FU during 21 days. Methods: Patients (p) with stage IV CRC, previously treated with oxaliplatin and CPT-11 for metastasic disease, ECOG  2, adequate bone marrow, renal and hepatic function. Schedule: 5FU 200 mg/m2 continuous intravenous infusion during 21 days every 28 days. Dose escalation: level 1: G 800 mg/m2; level 2: 1000 mg/m2; level 3: 1250 mg/m2 on Day 1 and 15. Results: 18 p were included, male:14 (76.5%), median age 63 (range 44–74) and ECOG 0–1 82.4%, ECOG 2: 17.6%. Previous treatment: surgery of primary disease +/- metastasectomy 76.5%, median number chemotherapy regimes: 2 (range 2–5); median number of metastatic sites: 2 (range 1–3). Median number of cycles: 6 (range 2–23). No grade 3/4 toxicity was observed in levels 1–2. In L3, Grade 3 was observed in 3/17 p: liver, neutropenia and diarrhea. Overall toxicity in L3 was G1 nausea in 1 p, G2 diarrhea in 1 p; G2 constipation 1 p, G1 hand-foot syndrome in 2 p, G1 anemia in 1 p; G2 anemia in 1 p; G1 hepatic toxicity in 3 p and 1 p with G1 mucositis. In only 3/17 p dose reduction was necessary. Objective responses were not seen but 12/17 p (70.5%) were evaluated as stable disease. Five/17 (29.5%) progressed during treatment. Clinical improvement as measured by symptoms was achieved in 10/17 p (58.8%). Median TTP was 112 days (range 44–396); with a median follow-up of 324 days (range 58–680). Twelve/18 p have already died with a median overall survival of 296 days (range 58–569). Conclusions: MTD was not reached during Phase 1, however the schedule administered in L3 is recommended, as it presents an adequate and manageable toxicity profile in this heavily pretreated group. Preliminary data show that this is an effective alternative in this setting of patients with no other standard active therapy.
No significant financial relationships to disclose.
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