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Objective: Combination therapy with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin is widely used for the treatment of metastatic colorectal cancer. However, little is known about the safety of chemotherapy of malignancies in hemodialysis (HD) patients. We encountered a patient with colorectal carcinoma on HD. We decided to administer combination chemotherapy while monitoring the pharmacodynamics of the patient. Case Report: A 74-year-old male received regular HD 3 times a week because of type 1 diabetes mellitus. He was diagnosed with stage IV colorectal cancer in November 2004. After sigmoidectomy, the patient received chemotherapy: a weekly schedule of CPT-11 (50 mg/m2) was administered followed by l-leucovorin (10 mg/m2) and 5-FU (400 mg/m2) just after HD. During the course, the plasma concentrations of both SN-38, an active metabolite of CPT-11, and 5-FU were not increased compared with those of patients with normal renal function. Our patient presented with grade III hematological toxicity that was easily recovered by granulocyte colony-stimulating factor. Conclusion: These data suggest that the dose-reduced Saltz regimen can be feasible for colorectal cancer patients receiving dialysis as postoperative adjuvant chemotherapy.

3562 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of IRIS to FOLFIRI, with progression-free survival (PFS) as the primary endpoint. We now report the final results of this study. Methods: The FIRIS study is a randomized, prospective, open-label, phase II/III study. Irinotecan (IRI)-naive mCRC patients with one prior chemotherapy regimen, ECOG PS 0–1, and adequate organ function were randomized to receive either FOLFIRI (200 mg/m2 of l-leucovorin given simultaneously with 150 mg/m2 of IRI, followed by a 400 mg/m2 bolus of 5-FU on day 1, and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or IRIS (125 mg/m2 of IRI on days 1 and 15, and 40–60 mg/body of S-1 twice daily for 2 weeks, followed by a 2-week rest). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), response rate (RR), safety, and treatment cost. Patient information was updated in July 2010. Results: At this final analysis, median follow-up was 3.1...

14538 Background: FOLFIRI is one of the standard regimens for MCRC. Considering the burden of continuous 5-FU administration, oral fluoropyrimidine-based therapy has been proposed in several clinical trials; however, gastrointestinal toxicity makes it difficult to perform successive oral chemotherapy. Therefore, no previous study could confirm whether to replace FOLFIRI with oral regimen. In order to find an appropriate schedule of oral fluoropyrimidine with safety and efficacy instead of continuous infusion of 5-FU, clinical trial using CPT-11, bolus 5-FU / l-LV and oral UFT / LV was conducted in pts with MCRC. Methods: Pts with MCRC, age > 18 years, ECOG PS 0–2, adequate organ function, and no or 1 prior chemotherapy were eligible. Pts received CPT-11 (100mg/m2) / 5-FU (500mg/m2) / l-LV (15mg/m2) i.v. on day 1 and UFT (300mg/m2) / LV (75mg/body) p.o. on days 1–5 (level 1), days 1–7 (level 2), or days 1–10 (level 3). Each course was repeated every 14 days. After determining feasible UFT / LV schedule, CPT-11 was dose-escalated (level 4: 125 mg/m2; level 5: 150mg/m2). Results: Nineteen pts were enrolled. A dose-limiting toxicity (DLT) of grade 4 neutropenia lasting for > 4 days was observed in 1 pt at level 2. Additional 3 pts at this level showed no toxicity of grade 3 or 4. A DLT of treatment delay (>8 days) was observed in 1 pt at level 3 because of prolonged neutropenia. Other 2 pts at level 3 refused to continue treatment within 4 cycles because of prolonged grade 2 anorexia. Obvious difference in toxicity was observed between level 2 and level 3. Therefore, 7-day-administration of UFT / LV was recommended. No DLT was observed at level 4 and 5, and the recommended dose of CPT-11 was 150mg/m2. The overall response rate was 66.7%. The median time to disease progression was 8.0 months. Conclusions: This oral fluoropyrimidine-based regimen is considered feasible and effective. The treatment schedule of UFT might be a key to prevent an early dropout due to gastrointestinal toxicity. Further study will be needed to confirm toxicity and efficacy of this regimen compared to FOLFIRI profile. No significant financial relationships to disclose.

3742 Background: A previous phase I trial in patients (pts) with metastatic colorectal cancer (CRC) demonstrated that weekly CPT-11 and bolus 5FU/l-LV administered for 3 weeks every 28 days (modifi...

3590 Background: Preoperative chemoradiotherapy is a cornerstone in patients (pts) with non-resectable LARC. To improve outcome (number of R0 resections and survival) radiotherapy (RT) was combined with oral UFT/l-leucovorin and a long delay to allow tumour regression before radical intended surgery. Methods: Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT pts received a daily dose of oral UFT 300 mg/m2 plus l-leucovorin 22.5 mg 5/7days (divided in three doses). Results: From April 1998 to June 2003, 50 pts (median age 61 years (31–83); median PS 0 (0–2) with LARC (34 primary, 16 recurrent) were treated. All pts received the planned 60 Gy...

3718 Background: This phase II study was undertaken to determine the efficacy of irinotecan plus weekly bolus 5-FU and high dose l-leucovorin for patients with metastasic colorectal cancer. Methods...

3705 Background: L-OHP has been established as a key drug for ACRC, and FOLFOX 4 is commonly used in Europe and the US. We conducted this trial to determine the recommended dose (RD) and evaluate safety and efficacy of L-OHP + weekly bolus 5-FU/l-LV as first-line treatment of ACRC. Methods: Inclusion criteria were unresectable ACRC, no prior chemotherapy, PS (ECOG) 0–2, age 20 - 75 years, measurable lesions, and adequate organ functions. L-OHP was administered over 2 hours (hrs) IV on days 1, and 15 with l-LV over 2 hrs IV and 5-FU IV bolus on days 1, 8, and 15 every 28 days. Doses of L-OHP and l-LV were fixed at 85 mg/m2 and 250 mg/m2 respectively, and that of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). RD was determined in a formal phase I dose escalation manner, and safety and efficacy were evaluated according to NCI-CTC v2.0 and RECIST guidelines. Results: No dose-limiting toxicity (DLT) was observed at level 1 (n = 3), but at level 2 (n = 4), 3 patients (pts) experienced DLTs ...

LV has a defined activity in the biochemical modulation of 5FU so that in ACC LV + 5FU is superior to 5FU alone in term of objective response (O.R.); the 5 days regimen with LD-LV appears active as HD-LV weekly administered. In this multicentric phase III study from 11/91 to 6/94, 422 patients (pts) were randomized between L LV 100 mg/sqm/iv x 5 d (arm A) versus L LV 10 mg/sqm/iv × 5 d (arm B). All pts received 5FU: 370 mg/sqm/iv × 5 d. Treatment was recycled every 28 d. Toxicity was acceptable in both groups with only 11% of pts experiencing grade 3–4 diarrhea and mucositis. At a median follow-up of 18 m, of 372 pts evaluable we observed similar activity: 20 OR (10.6%) in arm A (3 of them complete) and 21 (11.4%)OR in arm B, with 4 CR. No differences were observed in overall survival: 10 m for both groups. In this study HD- L LV and LD- L LV appear equally active in biochemical modulation of 5-d 5FU with lower costs for LD- L LV