Feasibility and tolerance of sequential chemoradiotherapy in squamous cell carcinoma of the head and neck

LOO S.W., GEROPANTAS K., TASIGIANNOPOULOS Z., MARTIN C. & ROQUES T.W. (2013) European Journal of Cancer Care 22 , 32–40 Feasibility and tolerance of sequential chemoradiotherapy in squamous cell carcinoma of the head and neck This paper evaluates the feasibility and tolerance of sequential chemoradiotherapy in patients with squamous cell carcinoma of the head and neck and ascertains whether the use of induction chemotherapy compromises delivery of subsequent radiotherapy with or without concurrent chemotherapy. We also compared sequential chemoradiotherapy treatment adherence between the elderly and younger patients with squamous cell carcinoma of the head and neck. One hundred and ninety-four patients with head and neck squamous cell carcinoma who received induction chemotherapy with cisplatin and 5-fluorouracil were included in this study. Treatment-related death rate from induction chemotherapy was 1.5%. One hundred and ninety-one patients (98.5%) proceeded to radical radiotherapy, with 90.1% also receiving planned concomitant chemotherapy. One hundred and seventy-eight patients (93.2%) completed radiotherapy with no prolongation of the treatment duration. There were no statistical differences in sequential chemoradiotherapy treatment adherence and tolerance between the elderly and younger patients apart from the proportion who required hospitalisation during radiotherapy. Induction chemotherapy in head and neck squamous cell carcinoma does not compromise delivery of definitive radiotherapy with or without concurrent chemotherapy. Elderly patients with head and neck squamous cell carcinoma are able to tolerate aggressive treatments such as sequential chemoradiotherapy. Treatment ‘deintensification’ based solely on chronological age is not recommended.     

Taxanes in the treatment of head and neck cancer

PURPOSE OF REVIEW: This review presents new data on the role of paclitaxel and docetaxel in the management of squamous cell carcinoma of the head and neck. Recently both agents have been tested in squamous cell carcinoma of the head and neck in combination with other chemotherapeutic agents, targeted drugs, and radiotherapy in in-vitro experiments and in the clinic as first-line treatment of patients with metastatic/recurrent and locally advanced squamous cell carcinoma of the head and neck. RECENT FINDINGS: The combination of taxanes with standard or accelerated radiotherapy is feasible and induction chemotherapy followed by chemoradiation is active and feasible without excessive toxicity in patients with locally advanced squamous cell carcinoma of the head and neck. The use of low-dose fractionated radiotherapy shows promising in-vitro and clinical results and is further explored. SUMMARY: Both docetaxel and paclitaxel can be combined with chemotherapeutic agents and radiotherapy, but phase III studies are needed to prove the superiority of these approaches compared to standard treatment. The final results of the combination study of cisplatin and 5-fluorouracil with or without docetaxel may change the standard chemotherapeutic regimen for induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck.     

Standard, and novel cytotoxic and molecular-targeted, therapies for HNSCC: an evidence-based review

(1) Head and neck squamous cell carcinoma is the sixth most frequently occurring cancer worldwide.(2) Chemotherapy has shown some success as part of multimodal treatment schedules for locally advanced, nonmetastatic head and neck squamous cell carcinoma, and too a much lesser extent for metastatic head and neck squamous cell carcinoma.(3) A recent meta-analysis of 32 studies involving >10,000 patients concluded that chemotherapy added to radiotherapy produces a large survival advantage relative to radiotherapy alone.(4) Concurrent or alternate chemoradiotherapy, with a schedule based on cisplatin, has an established place in the management of locally advanced nonmetastatic head and neck squamous cell carcinoma.     

Treatment of squamous cell carcinoma of the head and neck with multi-drug chemotherapy and radiotherapy

Multi-drug chemotherapy containing cisplatin has been reported to be one of the most active chemotherapy regimens in advanced or recurrent head and neck squamous cell carcinoma. In this study, the current status of clinical investigation of combination chemotherapies is reviewed. And our data are presented in head and neck cancer with multi-drug chemotherapy containing cisplatin. Thirty-five patients of stage 3-4 and 70 patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated by multi-drug chemotherapy containing cisplatin, and radiotherapy and/or operation. The overall response rate was 71.4%, with 17.1% complete remission in previously untreated, locally advanced patients and 31.4% in recurrent or metastatic patients. Problems of chemotherapy combined with radiotherapy and future direction of clinical study in locally advanced or recurrent head and neck cancer are discussed.     

Expanding role of the medical oncologist in the management of head and neck cancer

The multidisciplinary approach to treating squamous cell carcinoma of the head and neck is complex and evolving. This article aims to review some recent developments in squamous cell carcinoma of the head and neck, in particular the expanding role of chemotherapy in its management. Surgery and radiotherapy have remained the mainstay of therapy. Chemotherapy is increasingly being incorporated into the treatment of squamous cell carcinoma of the head and neck. Previously, radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced resectable disease. Data from randomized trials have confirmed the benefits of concurrent chemoradiotherapy in the adjuvant setting. Chemoradiotherapy is also the recommended approach for unresectable disease. Induction chemotherapy has been useful in resectable disease where organ preservation is desirable, but this approach was inferior for the goal of larynx preservation, while leading to similar survival when compared with concomitant chemoradiotherapy. There is recent evidence that taxanes added to induction chemotherapy with cisplatin and fluorouracil result in improved survival outcomes. Novel targeted agents, such as epidermal growth factor receptor antagonists, are showing promise in the treatment of patients with both locoregionally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck.     

Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: a phase II feasibility study

The purpose of this phase II feasibility trial was to determine the efficacy and toxicity of docetaxel combined with cisplatin and 5-fluorouracil in patients with locally advanced and/or recurrent squamous cell carcinoma of the head and neck. Nineteen patients entered the study. The majority had received prior radiotherapy but were chemotherapy naive. Treatment consisted of docetaxel 80 mg/m2 day 1, cisplatin 40 mg/m2 days 2 and 3, and 5-fluorouracil 1,000 mg/m2 by continuous infusion days 1 to 3. The cycle was repeated every 28 days. Most patients received granulocyte colony-stimulating factor, 150 microg/m2/day subcutaneously between days 4 and 8. The median number of chemotherapy cycles per patient was four. Dose reduction was done in three patients with no treatment delays. Of the 16 evaluable for response, seven patients (44%) demonstrated an objective response, including two complete and five partial ones; eight patients (50%) had stable disease; and one patient had progressive disease. The median time to progression was 7.5 months (range: 4-17.5 months). The median survival was 11 months (range: 1-18 months) and 1-year survival was 49%. Febrile neutropenia was recorded in 15% of courses. There were no toxic deaths. In conclusion, the combination of docetaxel, cisplatin, and 5-fluorouracil is an active regimen against previously treated squamous cell carcinoma of the head and neck with acceptable toxicity.     

Docetaxel and cisplatin: An active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck

Background: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.Patients and methods: Eligibility criteria included written informed consent, a WHO performance status <2, life expectancy of >12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3- antagonists, and corticosteroids.Results: Forty-four patients (median age 55 years, range 35–76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1–6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%–69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses.Conclusion: The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.     

Concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients (pts) with locally advanced head and neck cancer (HNC)

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.     

Three Weekly Versus Weekly Cisplatin as Radiosensitizer in Head and Neck Cancer: a Decision Dilemma

Cisplatin-based concurrent chemoradiation plays an undisputed key role as definitive treatment in unresectable patients with locally advanced squamous cell carcinoma head and neck or as an organ preservation strategy. Treatment with 100 mg/m2 3-weekly cisplatin is considered the standard of care but is often associated with several adverse events. The optimum drug schedule of administration remains to be defined and presently, there is insufficient data limiting conclusions about the relative tolerability of one regimen over the other. This review addresses regarding the optimal dose schedule of cisplatin focusing mainly on three-weekly and weekly dose of cisplatin based concurrent chemoradiotherapy in locally advanced head and neck cancer with an emphasis on mucositis, dermatitis, systemic toxicity, compliance, and treatment interruptions. To derive a definitive conclusion, large prospective randomized trials are needed directly comparing standard 3-weekly cisplatin (100 mg/m2) with weekly schedule (30 - 40 mg/m2) of concurrent cisplatin based chemoradiotherapy in locally advanced squamous cell carcinoma head and neck.     

Gemcitabine-based induction chemotherapy and concurrent with radiation in advanced head and neck cancer

To evaluate the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent gemcitabine and radiotherapy in advanced squamous cell carcinoma of head and neck. A total of 28 patients with locally advanced squamous cell carcinoma of the head and neck were enrolled. All patients were treated with 2 cycles of induction gemcitabine 1?gm/m² on days1 and 8 plus cisplatin 75?mg/m²no day 1 of a 3-week cycles followed by conventionally fractionated radiotherapy to 70?Gy in 35 fractions concurrent with weekly gemcitabine 100?mg/m² within 2?h before radiotherapy. Median age was 56.5?years (range, 30?C68). Four patients (14.3?%) achieved complete response (CR) and 19 patients (67.9?%) had partial response (PR) after induction chemotherapy. After concurrent chemo-radiotherapy, we reported 17 (60.7?%) CR and 8 (28.6?%) PR. Median loco-regional recurrence-free survival, progression-free survival, and overall survival were 17, 12.5, and 21?months, respectively. Performance status, T stage, AJCC stage, and response to chemo-radiation were found to have significant impact on survival. Acute grade 3 toxicity of concurrent chemo-radiation included 35.7?% dysphagia, 25?% stomatitis, and 10.7?% neutropenia, whereas late grade 3 toxicity included xerostomia in 7.1?% and stomatitis in 3.6?% of patients. Gemcitabine-based induction and concurrent chemo-radiotherapy is effective treatment for locally advanced squamous cell carcinoma of head and neck with acceptable and manageable toxicity. Optimizing dose and schedule of gemcitabine-based chemo-radiation is still needed.     

Phase I trial of dose-escalated cisplatin with concomitant cetuximab and hyperfractionated-accelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck

BackgroundCetuximab is active in the treatment of squamous cell carcinoma of the head and neck (SCCHN), enhancing both radiotherapy and chemotherapy effects. This phase I study was designed to investigate the safety and tolerability of combining weekly cisplatin treatment with cetuximab and hyperfractionated-accelerated radiotherapy (HART) for locally advanced SCCHN.Patients and methodsPatients with unresectable stage III or IVA/B SCCHN were treated with cetuximab, 400 mg/m² initial dose on day -7 of HART, followed by 250 mg/m² weekly during the administration of HART, which started with 2.0 Gy/day (5 days/week) for 3 weeks followed by 1.4 Gy/twice-daily (Monday to Friday) for another 3 weeks, resulting in a total dose of 70.6 Gy. Cisplatin was administered weekly starting on the first day of radiotherapy until week 6. Cisplatin was dose escalated of four dose levels from 20 to 40 mg/m² using a classical 3 + 3 dose escalation algorithm.ResultsEighteen patients were enrolled. Sixteen patients were eligible for toxicity, and 15 for response. No maximum tolerated dose was reached for cisplatin. One of six patients of dose level 4 had grade 4 neutropenia. This patient died 1 week after the end of the study treatment. The most common types of grade 3+ adverse events were mucositis (9 of 16 patients), in-field dermatitis (6 of 16 patients) and neutropenia (4 of 16 patients). Cetuximab-related hypersensitivity was observed in 1 out of 18 patients. Six weeks after the end of the study treatment, 5 complete responses, 8 partial responses and 1 progressive disease (at distant sites) were documented in a total of 15 patients (objective response rate 87%).ConclusionsThe combination of cisplatin with cetuximab and HART is active, well tolerated and merits additional investigation. The recommended weekly dose of cisplatin for phase II studies is 40 mg/m².     

Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel‐based radiochemotherapy

MENCOBONI M., GRILLO‐RUGGIERI F., SALAMI A., SCASSO F., REBELLA L., GRIMALDI A., DELLEPIANE M., MORATTI G., BRUZZONE A., SPIGNO F., GHIO R. & FIGLIOMENI M. (2010) European Journal of Cancer Care
Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel‐based radiochemotherapy Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty‐nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m² and cisplatin 75 mg/m² every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m². Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate >90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.     

Comparative Evaluation of Chemoimmunoradiotherapy and Chemoradiotherapy in the Management of Advanced Head and Neck Cancer

50 patients of advanced squamous cell carcinoma of the head and neck were randomised cither to receive chemotherapy followed by radiation therapy or chemoimmunotherapy followed by radiotherapy. In the chemoimmunotherapy arm, the patients received recombinant interferon alpha 2b 3 M.U. subcutaneously, thrice a week on alterante days for 5 weeks from Day 1, Cisplatinum 70 mg/ m² on Day 1 and 21, and 5 — flurouracil 1000mg/m² on Day 1, 2, 3 and Day 21, 22, 23, followed by from Dav 36, radiotherapy'by Co bait 60 to a tumour dose of 65 Gy in 30 # over 6 weeks. In the control arm, patiens received Cisplatitnum 70 mg/ m² on Day 1 and Day 21, 5 flurouracil 1000 mg/ m² on Dav 1, 2, 3 and Day 21, 22, 23 followed by radiotherapy by Cobalt 60 to a tumour dose of 65 Gy in 30 # over 6 weeks from Day 36. Only Grade II and III toxicity was observed in the two arms which were manageable Patients treated with chemoimmunotherapy followed by radiotherapy showed 60% complete response, 20% partial response and 12% no change/ progressive disease; while the patients on the control arm treated with chemotherapy and radiotherapy showed 12% complete response 44% Partial response and 32% no change“ progressive disease. This trial concludes that chemoimmunotherapy followed by radiotherapy is an excellent alternative therapeutic strategy for the management of advanced head and neck cancers with manageable toxicity.     

Continuous cisplatin (24-hour) and 5-fluorouracil (120-hour) infusion in recurrent head and neck squamous cell carcinoma

Cisplatin and 5-fluorouracil (5-FU) has been reported to be one of the most active chemotherapeutic regimens in recurrent head and neck squamous cell carcinoma. In this study, 21 patients with recurrent head and neck squamous cell carcinoma received a combination of cisplatin given as a 100 mg/m2 continuous infusion over 24 hours and 5-FU given as a 1000 mg/m2 24-hour continuous infusion for 120 hours. Toxicity was evaluated in all patients, and response and survival were evaluated 20 patients. There were two complete remissions (10%) and three partial remissions (15%) for a major response of 25%. Overall survival for the complete responders was 79+ and 61+ weeks, respectively. Median survival for all patients was 36 weeks. Toxicity consisted of moderate to severe nausea and vomiting in 14 patients (66%), mucositis in 14 patients (66%), granulocytopenia of less than 1000/microliter in 11 patients (52%), objective peripheral neuropathy in one patient (4.7%), and nephrotoxocity in one patient (4.7%). We conclude that the efficacy of 24-hour cisplatin infusion and 120-hour 5-FU infusion in the treatment of recurrent head and neck squamous carcinoma is not superior to the efficacy of single agent trials reported in the literature.     

Prospective pilot study of consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiotherapy for advanced head and neck cancer

PURPOSE: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. METHODS AND MATERIALS: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m(2), on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gy to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m(2), and cisplatin, 75 mg/m(2), every 3 weeks. RESULTS: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. CONCLUSION: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.     

Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial

BackgroundTo know the effectiveness and tolerance of weekly cisplatin added to radiotherapy (RT) in advanced carcinoma of oropharynx and nasopharynx.Patients and methodsStage II–IV cancer patients were randomly assigned to either radical RT, 70 Gy/35 fractions over 7 weeks (RT arm), or chemoradiotherapy (CRT), cisplatin 40 mg/m² weekly for seven doses plus RT. Primary end points were (i) the responses, (ii) toxicity profile, and (iii) overall survival (OS) in two groups. Study period was from June 2003 to July 2005.ResultsOne hundred and fifty-three patients were randomly allocated to the study, 76 in RT arm and 77 in CRT arm. Seventy-one in each arm completed the planned treatment; complete response (CR): 67.1% versus 80.5% in RT and CRT arms (P = 0.04). Grade III and IV toxicity were 16% and 40% in RT and CRT arms, respectively (P = 0.01). There were frequent treatment interruptions (9.3% versus 28.9%; P = 0.003) and hospitalization (20% versus 40.8%) in the CRT group. OS was superior in the CRT arm (P = 0.02): 27 months [95% confidence interval (CI) 15.2–36.8] for RT versus not reached for CRT. Three-year OS was 42% for RT and 62% for CRT group. CRT and CR were independent prognostic factors.ConclusionThis trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone resulting in higher OS.     

Concurrent chemoradiotherapy with low-dose cisplatin plus 5-fluorouracil for the treatment of patients with unresectable head and neck cancer

OBJECTIVE: The purpose of this study was to determine the efficacy of concurrent chemoradiotherapy using conventional radiotherapy combined with low-dose daily 5-fluorouracil (5FU) and cisplatin (CDDP) for the locally unresectable head and neck cancer patients. PATIENTS AND METHODS: From September 1996 through December 2000, we carried out a phase II study of concurrent chemoradiotherapy with low-dose CDDP plus 5FU for the treatment of patients with unresectable squamous cell carcinoma of the head and neck. Chemoradiotherapy consisted of irradiation with 1.6-2.0 Gy/day for 5 days per week up to a total dose 68 Gy and CDDP 3 mg/m2 by intravenous infusion over 1 h plus 5FU 150 mg/m2 by intravenous infusion over 24 h per day for 5 days per week. RESULTS: Ninety percent of the patients had stage IV disease, including 65% of patients with T4 disease. Thirty-three patients (83%) received the full treatment as planned; 39 (98%) received full-dose radiotherapy and 33 (83%) full-dose chemotherapy. Of the 40 patients evaluable for response, 20 (50%) achieved complete response (CR) and 12 (30%) partial response with an overall response rate of 80%. Among the 20 CR patients, 15 underwent endoscopic blind biopsies and 4 had positive lesions. The most frequently observed toxicity was mucositis. Ten patients developed grade III mucositis, and 3 patients required enteral nutritional support through a feeding tube. Grade III leukopenia, anemia and thrombocytopenia were observed in 28, 25 and 20% of the patients, respectively. The median duration of follow-up at the time of analysis was 18 months. The median survival time was 23 months. The responders survived longer (34 months) than the nonresponders (4 months; p < 0.05). CONCLUSION: This regimen is safe and efficacious in the treatment of patients with advanced unresectable head and neck cancer.     

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.     

Postoperative reduced dose of cisplatin concomitant with radiation therapy in high‐ risk head and neck squamous cell carcinoma

BACKGROUND:

The role of low doses of cisplatin and concomitant postoperative radiotherapy in high risk head and neck squamous cell carcinoma has not yet been defined.

METHODS:

Patients treated with definitive surgery, who had histological evidence of involvement of more than 2 lymph nodes, extracapsular extension of disease, perineural and/or intravascular invasion, involved or close surgical margins, received postoperative radiotherapy plus 75 mg/m² of cisplatin every 3 weeks during the radiotherapy cycle. The primary endpoints were to evaluate treatment compliance and overall, cause‐specific, and disease‐free survival.

RESULTS:

A total of 142 patients were enrolled. With a median follow‐up of 40 months, 5‐year overall survival was 68%, cause‐specific survival 78% and disease‐free survival 82%. At multivariate analysis surgical margins status and extracapsular lymph node invasion were the only statistically significant prognostic factors. Fifty‐three percent of the patients developed severe mucositis and 14% hematologic toxicity of grade 3. The 3 planned concomitant chemotherapy cycles were delivered to 48% of the patients.

CONCLUSIONS:

Postoperative radiotherapy and concomitant low‐dose cisplatin was an effective treatment in high risk head and neck patients. The total toxicity observed was lower compared with that reported with higher doses of cisplatin, although the delivery of all the 3 planned chemotherapy cycles was challenging. The distant failure rate was high, which was an unsatisfactory result. Cancer 2009. © 2009 American Cancer Society.     

Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase I trial

BackgroundStandard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN. Phase I study aims to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN.Patients and methodsInclusion criteria—SCCHN patients with T3 or T4 primary lesion (except T3N0 with negative resection margins); pathologic N2–N3 disease; poor prognostic findings; age 18–70 years; Eastern Cooperative Oncology Group performance status of zero to one; no evidence of metastasis; adequate organic function and written informed consent. Study design—dose-escalating phase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100–150 mg/day p.o.) and cisplatin (30–40 mg/m² i.v., day 1) for 7 weeks. Radiotherapy—standard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks.ResultsThirteen male (median age: 57 years) were enrolled. Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m²) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose for additional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m²/week i.v.ConclusionErlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo- or radiotherapy in this postsurgical population.