124 Addition of oxaliplatin (L-OHP®) to chronomodulated (CM) 5-fluorouracil (5-FU) and folinic acid (FA) for reversal of acquired chemoresistance in patients with advance colorectal cancer (ACC)

• Published in: European journal of cancer (1990) 1995-11, Vol.31, p.S29-S29
• Main Authors: Garufi, C., Bensmaïne, M.A., Brienza, S., Misset, J.L., Aschelter, A., Pace, R., Bertheault-Cvitkovic, F., Terzoli, E., Lévi, F.
• Format: Article
• Language: English
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/0959-8049(95)95379-K

L-OHP®/5-FU/FA CM combination partially circumvented 5-FU resistance in patients (pts) with ACC ( Cancer 1992, 69, 893). L-OHP® delivered as q 3 wks CM or bolus showed a 10% (14/138) overall response rate (ORR) in ACC pts with proven progressive disease (PD) while getting 5-FU/FA treatment. The non-cross resistance and/orsynergy of L-OHP® with 5FU/FA was assessed in 25 pts with acquired resistance (20 with CT scan-proven [PD]—and 5 with median 5 months [2.5–12] disease stabilisation [ST]) while on 5-day (d) CM 5-FU (700–1000 mg/sqm/d)/FA (300 mg/sqm/d) (peak delivery at 4.00 h) (FF). LOHP ® (20 to 25 mg/sqm/d, peak at 16.00 h) was added to this schedule in 2nd (12 pts) or 3rd line (13 pts) (FFL) according to 2 different schedules: 5d q 3 wks (14 pts) or 4 d q 2 wks (11 pts). Selection criteria: Pretreated ACC, no other intercurrent chemotherapy between the 2 schedules, measurable lesion. M/F = 10/15, median age = 59, colon/ŕectum = 14/11, PS 0-1 vs 2–3 = 22/3, nb of sites < 2 vs ≥ 2 = 8/17, liver involvement = 21 (94%). Previous 5-FU time exposition = median 7.2 months (1.5–25.2), FF (CM) median dose intensity (DI) = 1050 mg/sqm/wk. 17l cycles, median = 7 (1–15), time to exposition = 5 mo (1–9), 5-FU DI = median 1072 mg (831–1580), L-OHP® DI = median 35.7 mg (24–43). grade 3–4: nausea-vomiting = 25%, diarrhea = 16%, mucositis = 8%. No gr 3–4 hematotoxicity. No renal or auditive toxicity was observed. No toxic death. 7 PR (29.2%), 5 minor reponses (21%), 4 SD (17%) and 8 PD (33%). One pt too early. Duration of response was 8.5 mo, disease-free progression 5.8 mo and median survival 12 mo. Addition of L-OHP® can reversed FF resistance to CM 5-FU/FA in one third of pts. This further suggests a synergistic and/or modulatory effect between 5-FU and L-OHP®.