933 Oxaliplatin (L-OHP®): Global safety in 682 patients (PTS)

L-OHP ® is a Dach platinum with significant activity in pretreated advanced colorectal cancer. In order to describe its safety profile, we gathered the individual data of 682 patients (pts) who received 4303 cycles (cy) from 9 studies (seven phase II and two phase III). Treatment L-OHP ® was given as a single agent (SA, in 4 studies (40% of pts) and combined with 5-FU folinic acid (FFL) in 5 studies (60% ofpts). L-OHP ® was administered in 5 different schedules: 130 mg/sqm/dl iv over 2 hrs q3 wks in 37% ofpts, 130 mg/sqm/dl iv over 6 hrs q3 wks in 5% of pts, 100–200 mg/sqm continuous infusion (CI) over 5 days q3 wks in 20% of pts and 100–200 mg/sqm chronomodulated (CM) on 5 days q3 wks in 38% of pts. PT Characteristics Sex M/F: 63/37% PS (WHO) 0–1/2–3: 81/19%. Median age: 60 yrs. Tumor diagnosis: colorectal 80%, H&N 6%, melanoma 5%, other 9%. Pretreatment by chemotherapy (CT): 47%. Baseline abnormality grade (gr) 1–2: anemia 13%, WBC 3%, renal 2%, hepatic 88%, diarrhea 6%. Methodology Separate univariate and multivariate analyses were performed for single agent and combination studies, influence of the following prognostic factors was sought: age, sex, PS, previous CT, modality, renal baseline status. Each toxicity was evaluated according to the overall incidence (gr 1–4), severity (gr 3–4) and baseline status. Results (WHO and WHO modified scale) No drug related toxic death occurred. Global results are shown in the following table. Toxic effects Incidence Severity Prognostic factors (gr 1–4) (gr 3–4) SA FFL SA FFL Hematology 22% 35% 2% 6% Sex:F-PS:2-3 *** N-V * 65% 90% 11% 22% None Diarrhea 30% 85% 4% 25% None Neurologic ** 80% 83% 3% 19% Cumulative dose * With prophylactic antiemetic treatment. ** WHO modified scale. *** Anemia. Sensitive peripheral neuropathy is the most frequent limiting toxicity. Grade III neurotoxicity (functional impairment) appears in 12% of the pts at a median dose of 900 mg/sqm (range: 200–2525). According to Kaplan-Meier model, the risk of developing a severe neurotoxicity is: 10% after 6 cy (780 mg/sqm) and 50% after 9 cy (1170 mg/sqm). Its reversibility was evaluated after discontinuation in 78% of pts with ≥gr 2 neuropathy. Regression of symptoms was observed in 82% of these pts (median follow-up: 3–4 months) and disappearance for 41% of them (median follow-up: 6–8 months). Hematological and digestive toxicities were acceptable and caused discontinuation of the treatment in only 3 pts. Other severe toxicities were immediate intolerance (hypotension, faintness) in 1% of pts. There was no renal or auditive toxicity episode. Conclusion Oxaliplatin can be administered safely by CI, CM or 2–6 hrs infusion at 130 mg/sqm q3 wks. Its association with 5-FU/folinic acid does not enhance its toxicity as it is very well tolerated.