Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients

Head and neck cancer

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

BACKGROUND: Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease. METHODS: We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival. RESULTS: A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group. CONCLUSIONS: As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov].).

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Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer.

Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour–node–metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies. Head and neck squamous cell carcinomas (HNSCCs) originate from the mucosal epithelium in the oral cavity, pharynx and larynx and are commonly associated with viral infection and tobacco use. This Primer provides an overview of the epidemiology, pathogenesis and treatment of HNSCCs of different aetiologies and the effects of the cancer and its treatment on patient quality of life.

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Head and neck squamous cell carcinoma

Background A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy. Methods We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival. Results With a minimum of 2 years of follow-up (≥3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There...

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Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.

BACKGROUND
Seminal trials have demonstrated improved survival in pancreatic adenocarcinoma with novel multiagent chemotherapy regimens. To understand the clinical ramifications of this paradigm shift, we reviewed our institutional experience.


METHODS
This retrospective cohort study utilized a prospective database at a single institution to study all patients diagnosed with and treated for pancreatic adenocarcinoma between 2000 and 2020.


RESULTS
1,572 patients were included of which 36% were diagnosed before (Era 1) and 64% after (Era 2) 2011. Survival improved in Era 2 (Median survival 10 vs 8 months, HR .79; P < .001). The survival advantage for Era 2 was primarily seen in patients with high-risk disease (12 vs10 months, HR .71; P < .001). A similar trend was noted for patients undergoing surgical resection (26 vs 21 months, HR .80; P = .081) and with imminently resectable tumors (19 vs 15 months, HR .88; P = .4); however, this was not statistically significant. There was no survival advantage for patients with stage IV disease (4 vs 4 months). Patients in Era 2 were more likely to undergo surgery (OR 2.78; CI 2.00-3.92, P < .001). This increase was driven primarily by increased surgical resection for those with high-risk disease (42 vs 20%, OR 3.74; P < .001).


DISCUSSION/CONCLUSIONS
This single institutional study showed improved survival after the shift to novel chemotherapy regimens. This was driven by improved survival for patients with high-risk disease and may be due to more effective eradication of microscopic metastatic disease with adjuvant chemotherapy and increased resection rates.

Matthew Dugan

Papers

Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.

Improved Overall Survival of Patients with Pancreatic Cancer through Multiagent Chemotherapy and Increased Rates of Surgical Resection.