Oral vinorelbine-based concomitant chemoradiotherapy in unresectable stage III non-small cell lung cancer: a systematic review.

INTRODUCTION: Cisplatin-based chemotherapy administered concomitantly to thoracic radiotherapy is the treatment recommended by the European guidelines for fit patients with unresectable stage III non-small cell lung cancer (NSCLC). Cisplatin may be combined with etoposide, vinorelbine or other vinca alkaloids, which act also as radiation sensitizers. Initially administered intravenously, vinorelbine is also available as oral formulation and is the only orally available microtubule-targeting agent. In addition, the oral formulation avoids the risk of extravasation and phlebitis. Areas covered: A literature search has been performed for articles reporting phase II-III trials aimed to evaluate efficacy and safety of oral vinorelbine-based chemoradiotherapy in unresectable locally advanced NSCLC. Expert commentary: In a series of trials with various protocols published from 2008 to 2018, mostly phase II studies, oral vinorelbine demonstrated a significant activity in concomitant chemoradiotherapy for unresectable locally advanced NSCLC typically as part of combination schedules with cisplatin. Main toxicities were hematologic (neutropenia and anemia); non-hematological toxicities included esophagitis and gastro-duodenal adverse events. Large prospective phase III trials are needed to confirm the role of vinorelbine-based chemotherapy associated to thoracic radiotherapy in unresectable stage III NSCLC and more particularly trials with metronomic oral vinorelbine.

Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: tolerance and efficacy.

BACKGROUND: Rectal cancer predominantly affects the elderly. Unfortunately, this age category is under-represented in clinical trials because clinicians are loath to include patients with a high risk of comorbidity. PATIENTS AND METHODS: An exploratory analysis of the ACCORD12/PRODIGE 2 phase III trial was carried out to retrospectively compare the benefit of neoadjuvant chemotherapy between the elderly (≥70 years; n=142) and younger patients (<70 years; n=442), this analysis was not preplanned in the study protocol. Patients with histologically confirmed resectable stage T3 or T4 rectal adenocarcinoma were eligible with an age limit of 80 years. RESULTS: Overall, the two age categories did not statistically differ in terms of patient's clinical and tumor baseline characteristics. Preoperative chemoradiotherapy leads to more severe grade 3/4 toxicities (25.6% vs. 15.8%, p=0.01) and more permanent stomas (33.3% vs. 22.8%, p=0.014) in elderly patients who were less often operated on than younger patients (95.8% vs. 99.0%, p=0.008). The relative number of interventions per surgery type (p=0.18), treatment efficacy in terms of R0 resection rate (88.6% vs. 90.6%; p=0.54) and complete pathological response (14.7% vs. 16.9%; p=0.55) were nearly identical between the two categories. CONCLUSION: Altogether these results warrant the development of specific optimal therapeutic strategies for the elderly.

Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2.

PURPOSE: Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. PATIENTS AND METHODS: We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). RESULTS: Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). CONCLUSION: The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.