Systemic therapy in the curative treatment of head and neck squamous cell cancer: A systematic review

Abstract

ObjectiveTo review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in patients with locally advanced nonmetastatic (Stage III to IVB) squamous cell carcinoma of the head and neck (LASCCHN).MethodRecognizing the Meta-analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) group reports have de facto guided practice since 2000, we searched for systematic reviews in the MEDLINE, EMBASE and Cochrane Database of Systematic Reviews published from January 2000 to February 2015 in reference to 4 research questions. A search was also conducted for randomized trials (RCTs) up to February 2015 not included in the meta-analyses.ResultThe MACH-NC reports, 5 additional meta-analyses, and 30 RCTs not included by MACH-NC were identified. For chemotherapy, MACH-NC findings showing improved overall survival with concomitant chemoRT did not require modification. High-dose cisplatin was most commonly studied. We confirmed this benefit with cisplatin monotherapy in patients treated with with postoperative concurrent chemoRT. Other than cetuximab, no targeted agents and radiosensitizers studied in RCTs were shown effective. TPF induction chemotherapy was superior to PF for tumor response and larynx preservation but not survival. Larynx preservation was reported with both CRT and induction chemotherapy approaches.ConclusionChemoRT with cisplatin at least 40 mg/m2 per week given as radical or postoperative adjuvant remains a standard treatment approach for LASCCHN that improves overall survival but increases toxicity. 5-FU plus platinum is supported by less data but may be a reasonable alternative for patients unsuitable for cisplatin. Of note, stratification of outcomes by HPV-status was not available but outcomes for oropharynx cancer appeared similar to other subsites in chemoRT RCTs. No RCTs have yet demonstrated superiority or non-inferiority of cetuximab-RT to CRT. In view of this, cetuximab-RT is suggested only for patients not candidates for CRT. Taxane-based triplet induction chemotherapy is superior to doublets for rapid tumour downsizing and for larynx preservation, but does not improve overall survival and should be used with primary G-CSF prophylaxis. Further investigation of induction approaches for larynx preservation may be warranted.

Treatment deintensification in human papillomavirus‐positive oropharynx cancer: Outcomes from the National Cancer Data Base

“…Access to this information would have provided a key additional control as it may be an important variable for the stratification of patient outcomes after de‐escalated treatment combinations. Lack of specific chemotherapeutic agent data also is limiting given the particular benefit of cisplatin for this disease . Finally, although HPV testing can be quite accurate, its accuracy can vary by the used diagnostic test .…”

“…Lack of specific chemotherapeutic agent data also is limiting given the particular benefit of cisplatin for this disease. 45 Finally, although HPV testing can be quite accurate, its accuracy can vary by the used diagnostic test. 46 This highlights the importance of the testing laboratory and its experience with this form of diagnostic testing.…”

Radiotherapy vs surgery for T1‐2N0M0 laryngeal squamous cell carcinoma: A population‐based and propensity score matching study

“…Depending on the disease stage at diagnosis, the primary management strategies for patients with laryngeal squamous cell carcinoma (LSCC) mainly consist of surgery and/or radiotherapy. Although the cure rate for early‐stage (T1‐2N0M0) LSCC is favorable, and ranges between 60% and 100% in several studies, the optimal treatment strategy has not been determined . According to the latest NCCN guidelines, surgery or definitive radiotherapy can be used for curing T1‐2N0M0 LSCC.…”

Local immune parameters as potential predictive markers in head and neck squamous cell carcinoma patients receiving induction chemotherapy and cetuximab

“…TPF (docetaxel, cisplatin, 5‐fluorouracil) induction chemotherapy was proved more effective compared to the PF (cisplatin, 5‐fluorouracil) regimen . However, the value of the addition of induction chemotherapy to radiotherapy or chemoradiotherapy in terms of improving overall survival is controversial . Addition of cetuximab to this regimen may theoretically increase efficiency as it does when used concomitantly with radiotherapy or combined with chemotherapy for the palliative treatment of recurrent/metastatic disease, usually at the cost of increased toxicity .…”

“…4,5 However, the value of the addition of induction chemotherapy to radiotherapy or chemoradiotherapy in terms of improving overall survival is controversial. [6][7][8] Addition of cetuximab to this regimen may theoretically increase efficiency as it does when used concomitantly with radiotherapy or combined with chemotherapy for the palliative treatment of recurrent/metastatic disease, usually at the cost of increased toxicity. 9,10 Hence, it is important to search for biomarkers allowing prospective identification of patients likely to derive benefit from the therapy.…”