A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX.
What this study found
The formula did not reduce severe oral mucositis during chemoradiotherapy, and overall survival or progression-free survival were not significantly improved in the full study population. During treatment, grade 3-4 mucositis was similar between groups by RTOG (33.7% vs 34.9%) and WHO (34.9% vs 33.7%) scales, with no difference one month after CRT. In the overall analysis at 3 years, OS was 77% versus 68% (P = 0.261) and PFS was 70% versus 59% (P = 0.138) for immunonutrients versus control. In the subgroup with ≥75% compliance (n = 112), 3-year OS was 81% versus 61% (P = 0.034) and PFS was…
- Study & population
- This was a double-blind phase III multicenter trial in adults with head and neck squamous cell carcinoma after surgery who were eligible for postoperative chemoradiotherapy.
- Intervention
- The active regimen was an oral immunomodulating nutritional formula (Oral Impact) enriched with L-arginine, omega-3 fatty acids, and ribonucleic acids.
- Key limitation
- The main endpoints were negative in the intention-to-treat analysis, so the overall efficacy signal was weak.
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Open PDFOriginal abstract
BACKGROUND In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. OBJECTIVES The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. METHODS Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. RESULTS At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P = 0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012). CONCLUSIONS Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.