Details

Autor(en) / Beteiligte

• Bensadoun, René-Jean
• Etienne, Marie-Christine
• Dassonville, Olivier
• Chauvel, Pierre
• Pivot, Xavier
• Marcy, Pierre-Yves
• Prevost, Bernard
• Coche-Dequeant, Bernard
• Bourdin, Sylvain
• Vallicioni, Jacques
• Poissonnet, Gilles
• Courdi, Adel
• Teissier, Eric
• Lagrange, Jean-Léon
• Thyss, A
• Santini, José
• Demard, François
• Schneider, Maurice
• Milano, Gérard

Titel

Concomitant B.I.D. radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in unresectable squamous-cell carcinoma of the pharynx: clinical and pharmacological data of a French multicenter phase II study

Ist Teil von

• International journal of radiation oncology, biology, physics, 1998-09, Vol.42 (2), p.237-245

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Purpose: The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)–5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic–pharmacodynamic relationships were analyzed. Methods and Materials: Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2–day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care. Results: Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3–4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC0-105h were significantly linked to grade 3–4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival. Conclusion: This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.