Weekly Oxaliplatin, High-Dose Folinic Acid and 24h-5-fluorouracil (FUFOX) as Salvage Therapy in Metastatic Colorectal Cancer Patients Pretreated with Irinotecan and Folinic Acid/5-Fluorouracil Regimens

 

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Zusammenfassung

Irinotecan (CPT-11), Oxaliplatin (OXA) und Kombinationen von Folinsäure (FA) und 5-Fluorouracil (5-FU) sind aktive Substanzen in der Erst- und Zweittherapie des metastasierten kolorektalen Karzinoms. Bisher ist jedoch unklar, ob und von welcher Sequenz diese Patienten in der Zweit- und Dritttherapie am ehesten profitieren. Nach Erst- und Zweittherapie mit CPT-11 gibt es gegenwärtig keine evidenzbasierten Daten zu Folgeprotokollen. Daher untersuchten wir retrospektiv Nebenwirkungen, Ansprechrate und Gesamtüberleben von Patienten, die ambulant mit der wöchentlichen Kombination von Oxaliplatin und hochdosierter Folinsäure mit 5-Fluorouracil (FUFOX) nach zwei unterschiedlichen CPT-11-haltigen Protokollen behandelt wurden.

Patienten: Von Oktober 1999 bis Mai 2001 wurden 20 Patienten (Median 62; 48-74 Jahre) eingeschlossen, die unter Vortherapie progredient waren. 7 Patienten erhielten initial CPT-11/Bolus-FA/5-FU (gemäß Saltz, Gruppe A), 13 Patienten initial FA/5-FU und danach CPT-11 Mono (Gruppe B). Das Protokoll war OXA (60 mg/m²), FA (500 mg/m²), 5-FU (2,6 g/m², 24h-Port-Infusion), Tag 1, 8, 15, 22, danach 2 Wochen Pause.

Ergebnisse: 252 Gaben FUFOX wurden ambulant verabreicht (1203 mg Dosis OXA/Pat). Bei 10 Patienten traten Toxizitäten NCI-CTC-Grad 3 auf: 4 × Diarrhö, 5 × Mukositis, 2 × Übelkeit/Erbrechen, je 1 × Anämie, Thrombopenie, Leukopenie bzw. Hand-Fuß-Syndrom. Drei Patienten zeigten minimale Remission, 11 Patienten stabilen Krankheitsverlauf. Das mediane Überleben ab Beginn von FUFOX war 33 (i. r. 5-65), die mediane progressionsfreie Zeit lag bei 16 (0-39) Wochen. Das Gesamtüberleben ab Beginn der palliativen Ersttherapie war 99 (44-200) Wochen.

Schlussfolgerungen: FUFOX erreichte bei akzeptablem Toxizitätsprofil eine Tumorkontrolle in 70 % und bei individuellen Patienten eine Lebensverlängerung. Nach FA/5-FU- und CPT-11-Vorbehandlung ist FUFOX eine wirksame Therapieoption des metastasierten kolorektalen Karzinoms.

Abstract

Irinotecan (CPT-11), oxaliplatin (OXA) and different folinic acid (FA) modulated 5-fluorouracil (5-FU) regimens are active as first- and second-line chemotherapy of metastatic colorectal cancer. However, the best palliative sequence of these substances is still unclear. After CPT-11 containing regimens the optimal salvage protocol has not yet been defined. Here, we retrospectively analysed the weekly ambulant combination of OXA with continuous FA/5-FU (FUFOX) after two different CPT-11 containing chemotherapeutic regimens.

Patients: During October 1999 and May 2001, 20 patients (median 62; 48-74 years) were included who had disease progression after CPT-11/bolus FA/5-FU (Saltz; 7 patients, group A) or after FA/5-FU followed by CPT-11 alone (13 patients, group B). OXA (60 mg/m²) was given for 2 hours prior to FA (500 mg/m²) as 2 h-infusion and continuous 5-FU (2.600 mg/m²) for 24 h-infusion on day 1, 8, 15 and 22 (repeated after week 6).

Results: FUFOX was administered 252 times. About 1,203 mg OXA per patient was given. Toxicities NCI-CTC grade 3 were observed in 10 patients: diarrhoea (4), mucositis (5), nausea/vomiting (2), anaemia (1), leucopenia (1), thrombopenia (1) and hand-foot-syndrome (1). 3 patients showed minor remissions, 11 patients stable disease. The median time to progression was 16 (0-39) weeks. The median survival from start of FUFOX and from start of any palliative therapy was 33 (5-65) and 99 (44-200) weeks for all patients, respectively.

Conclusions: FUFOX was efficient for additional tumour control in 70 % of patients pretreated with CPT-11/5-FU based regimens. Sequential palliative treatment can lead to prolonged survival.

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Dr. Markus Moehler

Johannes-Gutenberg-University of Mainz, 1. Dept. Internal Medicine

Langenbeckstraße 1

55101 Mainz

Email: moehler@mail.uni-mainz.de