{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:46:32Z","timestamp":1791013592940,"version":"4.1.0"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1999,6]]},"abstract":"<jats:p> PURPOSE: Two phase I studies of the oxaliplatin and irinotecan combination were performed in advanced gastrointestinal cancer patients to characterize the safety and pharmacokinetics of the regimen. <\/jats:p><jats:p> PATIENTS AND METHODS: Patients with a performance status (PS) of \u22642 and normal hematologic, hepatic, and renal functions received oxaliplatin (2-hour intravenous infusion) followed 1 hour later by irinotecan administered over a 30-minute period, every 3 weeks. Dose levels that were explored ranged from 85 to 110 mg\/m<jats:sup>2<\/jats:sup> for oxaliplatin and 150 to 250 mg\/m<jats:sup>2<\/jats:sup> for irinotecan. Plasma pharmacokinetics of total and ultrafiltrable platinum, irinotecan, SN-38, and its glucuronide, SN-38G, were determined. <\/jats:p><jats:p> RESULTS: Thirty-nine patients with gastrointestinal carcinomas (24 with colorectal cancer [CRC], four with pancreas cancer, four with gastric cancer, three with hepatocarcinoma, and four with other) received 216 treatment cycles. Median age was 54 years (range, 21 to 72 years); 95% had PS of 0 to 1; all but six had failed fluorouracil (5-FU) chemotherapy. The maximum-tolerated dose was oxaliplatin 110 mg\/m<jats:sup>2<\/jats:sup> plus irinotecan 200 mg\/m<jats:sup>2<\/jats:sup> in one study and oxaliplatin 110 mg\/m<jats:sup>2<\/jats:sup> plus irinotecan 250 mg\/m<jats:sup>2<\/jats:sup> in the other study. Grade 3 to 4 diarrhea and febrile neutropenia were dose-limiting toxicities; other toxicities included emesis and dose-cumulative neuropathy. Recommended dose for phase II studies is oxaliplatin 85 mg\/m<jats:sup>2<\/jats:sup> and irinotecan 200 mg\/m<jats:sup>2<\/jats:sup>. At this dose (12 patients, 65 cycles), grade 3 and 4 toxicities per patient included the following: emesis in 42% of patients, neutropenia in 33% (febrile episodes in 17%), peripheral neuropathy in 25%, delayed diarrhea in 17%, and thrombocytopenia in 8%. Two patients with Gilbert's syndrome experienced severe irinotecan toxicity. No plasmatic pharmacokinetic interactions were detected. Seven partial responses were observed in 24 CRC patients. <\/jats:p><jats:p> CONCLUSION: This combination is feasible, with activity in 5-FU\u2013resistant CRC patients. Phase I studies that explore the every-2-weeks schedule, in addition to phase II studies of this schedule (as well as in combination with 5-FU) as second-line therapy of metastatic CRC, are ongoing. <\/jats:p>","DOI":"10.1200\/jco.1999.17.6.1751","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:13:07Z","timestamp":1487916787000},"page":"1751-1751","source":"Crossref","is-referenced-by-count":104,"title":["Combination of Oxaliplatin Plus Irinotecan in Patients With Gastrointestinal Tumors: Results of Two Independent Phase I Studies With Pharmacokinetics"],"prefix":"10.1200","volume":"17","author":[{"given":"Ernesto","family":"Wasserman","sequence":"first","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cuvier","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Lokiec","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Goldwasser","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"Kalla","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"M\u00e9ry-Mignard","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Ouldkaci","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amine","family":"Besmaine","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Dupont-Andr\u00e9","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mondher","family":"Mahjoubi","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Marty","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; H\u00f4pital Saint-Louis, Paris; Centre Ren\u00e9 Huguenin, Saint-Cloud; Bellon\/Laboratoires Rh\u00f4ne-Poulenc Rorer, Montrouge; Sanofi-Winthrop, Gentilly; and Cvitkovic & Associ\u00e9s Consultants, Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Misset","sequence":"additional","affiliation":[{"name":"From the H\u00f4pital Paul Brousse, Villejuif; 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