The impact of cumulative dose of cisplatin on outcome of patients with head and neck squamous cell carcinoma

Abstract

Despite the wide use of cisplatin-based concomitant chemoradiotherapy (CCRT) for head and neck squamous cell carcinoma (HNSCC), data on the optimal regimen and cumulative dose are scarce and frequently conflicting. We aimed to evaluate the compliance and the impact of the cumulative dose of cisplatin on overall survival (OS), disease-free survival (DFS), loco-regional control (LRC), and distant-metastasis-free survival (DMFS) in a retrospective study. Between 2008 and 2015, 279 patients with HNSCC scheduled for CCRT (three courses of 3-week 100 mg/m cisplatin) were identified. Of the whole group, 14% did not receive any cisplatin and 26% received daily cisplatin. In patients planned for three courses (n = 167), 56% received 3, 20% received 2, and 24% received one course. After median follow-up of 31.6 months, the actuarial OS, DFS, LRC, and DMFS rates at 3 years for patients received cumulative dose of ≥200 mg/m were significantly better compared to those received <200 mg/m; 74 vs. 51% for OS, 73 vs. 49% for DFS, 80 vs. 58% for LRC (p < 0.001), and 85 vs. 76% for DMFS (p = 0.034). At multivariate analysis, the cumulative cisplatin dose (≥200 vs. <200 mg/m) was significantly predictive for OS (HR 2.05; 95% CI 1.35-3.13, p = <0.001). Borderline GFR (60-70 mL/min) at baseline predicts compliance for ≥two courses (p = 0.003). In conclusion, considerable proportion of patients did not receive all pre-planned courses of cisplatin. Patients receiving cumulative cisplatin dose ≥200 mg/m had significantly better outcome than those receiving <200 mg/m and cumulative dose <200 mg/m might even be detrimental. These findings increased the bulk of slowly growing evidence on the optimal cumulative dose of cisplatin. Baseline GFR might predict compliance.

Drug Sensitivity Prediction Models Reveal a Link between DNA Repair Defects and Poor Prognosis in HNSCC

“…For this purpose, we used pretreatment tumor biopsy gene expression data from our in-house HNSCC cohort (NKI-CRAD) of 98 patients with advanced stage HPV-negative tumors (characteristics in Supplementary Table S4), who underwent radiotherapy with cisplatin-based treatment regimens. Consistent with previous reports, tumor site (31) and cumulative cisplatin dose (32) are prognostic factors in our NKI-CRAD cohort. DNA repair defect scores were established using the mmcOnly model ensemble for all tumor samples.…”

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation

“…Clinical factors were tested for their association with locoregional control and other survival outcomes ( Supplementary Figure 1, Supplementary Table 1). Consistent with previous reports we find that locoregional control (LRC) is influenced by cumulative cisplatin dose levels (66,67). The cumulative cisplatin dose of < 200 mg/m 2 BSA was significantly associated with LRC failure (HR = 2.57, p = 0.0012).…”

“…Not all patients completed the full chemotherapy scheme. Therefore, cumulative cisplatin doses were calculated and patients were classified into < or ≥ or 200 mg/m 2 BSA cisplatin, according to literature (66,67). Survival data was calculated from the start of treatment until the first event was detected.…”

Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin

“…There are consensus that RT alone is less effective than platinum-based CRT [13] . Furthermore, patients receiving cumulative dose of < 200 mg/m2 had significantly worse outcome than those receiving > 200 mg/m2 [14] . Therefore, we excluded the patients who received RT alone or reduced dose of CDDP plus RT.…”