Clinical phase II evaluation of paclitaxel in combination with cisplatin in metastatic or recurrent squamous cell carcinoma of the head and neck

Background: Paclitaxel as single agent has shown marked activity in several malignancies. The aim of the present phase II trial was to determine the activity of paclitaxel/cisplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck.Patients and methods: 200 mg/m² paclitaxel was administered over three hours followed by cisplatin (100 mg/m²), repeated every 22 days. Twenty-eight patients were entered and received a total of 99 cycles (median 2, range 1–6). All patients were evaluable for toxicity, and 25 for response.Results: Hematologic toxicities included leukopenia CTC grade 3 in 13 patients, and grade 4 in five patients, neutropenia grade 3 in nine patients, and grade 4 in eigth patients, grade 3 anemia and grade 2 thrombocytopenia in one patient each. Non-hematologic toxicities included hypotension grade 2 (six patients), grade 3 (four patients), and grade 4 (two patients). A decline in renal function was observed in 15 courses and 10 patients, leading to a median delay of 2.5 days. Neurosensory and neuromotor toxicity grade 1 were observed in 13 patients (grade 2: 12 patients; grade 3: one patient), myalgia grade 3 in one patient, asthenia grade 3 in two and grade 4 in one patient. Partial responses were observed in 12 patients for an overall response rate of 48% (95% CI: 28%–68%) with a median response duration of 6.5 months (range 1-10 months). Stable disease was observed in seven patients, of who two also had clinical benefit.Conclusions: Paclitaxel 200 mg/m² administered over three hours combined with cisplatin 100 mg/m² is an active regimen warranting further evaluation.     

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.

PURPOSE: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions. RESULTS: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level II; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54, 41 and 31%, respectively. CONCLUSIONS: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.     

An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

Background: Vinorelbine is an active drug in the treatment of lung and breast cancers and has a favorable toxicity profile. Many clinical trials have demonstrated its antitumor activity in other tumor types including squamous cell carcinoma of the head and neck (SCCHN). We investigated the efficacy and tolerability of vinorelbine in patients with recurrent and/or metastatic SCCHN, previously untreated by chemotherapy.Patients and methods: Seventy-one patients with locoregional recurrent and/or metastatic SCCHN were treated with vinorelbine at a dose of 30 mg/m2/week i.v. by short-duration infusion on an out-patient basis. Doses were adjusted according to tolerance.Results: Two complete and seven partial responses were observed among 56 evaluable patients, yielding a response rate of 16% (95% confidence interval (CI): 8%–28%). The overall response rate of all eligible patients (63) was 14%. The responses were seen in recurrent tumors, lymph nodes and in lung metastases, and their median duration was 19 weeks (12–63). The main toxicity, severe and reversible neutropenia (grade 3–4) occurred in 53% of the 69 evaluable (for toxicity) patients. Twelve patients developed severe bronchopulmonary infections, which caused two early deaths. Constipation was observed in 31 patients (45%). Other gastrointestinal toxicities, asthenia, acute pain syndrome and peripheral sensory neuropathy, were mild to moderate. The median number of treatments was seven cycles and the median relative dose intensity of vinorelbine was 85% (25.5 mg/m2/week).Conclusions: Vinorelbine is an active drug, with acceptable toxicity, in recurrent and/or metastatic SCCHN, at the dose and schedule administered in the present study. Further evaluation in association with other agents and/or radiotherapy is warranted.     

Docetaxel and cisplatin in locally advanced or metastatic squamous-cell carcinoma of the head and neck: A phase II study of the Southern Italy Cooperative Oncology Group (SICOG)

Background:Docetaxel is one of the most promising new drugsagainst squamous-cell carcinoma of the head and neck (SCCHN), while cisplatinis one of the most active single agents. A phase I study has shown thefeasibility of the combination of the two drugs, and activity in SCCHN hasbeen seen. Patients and methods:Patients with locally advanced, inoperable,or metastatic SCCHN, never pretreated with radiotherapy or chemotherapy,received three courses of docetaxel 75 mg/m² and cisplatin 100mg/m², every three weeks. Thereafter, responsive metastaticpatients received additional chemotherapy, while patients with locallyadvanced disease underwent radiation therapy. Results:Forty-six patients (forty-five with locally advanced, onewith metastatic disease) were entered into the study. Ten patients did notcomplete three courses of chemotherapy because of early death; one patientdiscontinued treatment after one course. Twenty-one objective responses wereobserved (46%, 95% confidence interval (CI):31%–60%), including five complete responses (11%)and sixteen partial responses (35%). Following induction chemotherapyplus radiation therapy, 9 of 21 evaluable patients were rendered disease free,while 8 additional patients had a partial response. After a median follow-upof 18 months, the median duration of response was 12 months, (range3–25+), and the median overall survival was 11 months. Six early deathswere considered possibly treatment-related (sepsis following grade 4neutropenia in two cases, hypovolemic shock following severe diarrhea in fourcases). Neutropenia was the most severe toxicity (grade 3–4 in 28patients, median duration 4 days); diarrhea and vomiting were the mosttroublesome non-haematologic toxicities (grade 4 in 4 and 3 patients,respectively). Conclusions:The combination of docetaxel and cisplatin is activein SCCHN, but toxicity is substantial. This schedule does not appear to offerany advantage compared with conventional regimens.     

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck.

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m(-2) by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1-9) per patient. The median cumulative dose was 449 mg m(-2). Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1-50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4-52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h(-1) m(-2) and an area under the curve of 6.00 microg ml(-1) h(-1) was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance.     

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

We aimed to evaluate the efficacy and safety of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 37 patients with stage III or IV SCCHN were enrolled on the study. The chemotherapy consisted of two cycles of intravenous cisplatin of 80 mg m(-2) on day 1 and oral capecitabine 825 mg m(-2) twice daily from day 1 to day 14 at 3-week intervals. The radiotherapy (1.8-2.0 Gy 1 fraction day(-1) to a total dose of 70-70.2 Gy) was delivered to the primary tumour site and neck. The primary tumour sites were as follows: oral cavity (n=6), oropharynx (n=11), hypopharynx (n=8), larynx (n=3), nasopharynx (n=6), and paranasal sinus (n=3). After the chemoradiotherapy, 29 complete responses (78.4%) and 6 partial responses (16.2%) were confirmed. Grade 3 or 4 neutropenia occurred only in two patients, plus grade 3 febrile neutropenia was observed only in one patient. At a median follow-up duration of 19.8 months, the estimated overall survival and progression-free survival rate at 2-year was 76.8 and 57.9%, respectively. Concurrent chemoradiotherapy with capecitabine and cisplatin was found to be well tolerated and effective in patients with locally advanced SCCHN.     

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin-5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel-PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and overall response rates were demonstrated across the phase II trials in the range 42-82 and 71-100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and overall response of patients treated with docetaxel-based induction chemotherapy.     

Single-agent docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN)

BACKGROUND: The objective of this retrospective study was to investigate the efficacy and tolerability of single-agent docetaxel in patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS: Platinum-refractory disease was defined as cancer with documented tumor progression during platinum-based treatment or recurrence within 6 months after platinum-based chemoradiotherapy. Patients fulfilling the following criteria were enrolled: histologically confirmed SCCHN, excluding nasopharyngeal cancer; measurable metastatic lesions as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST); and platinum-refractory disease. Docetaxel (60 mg/m2) was administered every 3-4 weeks and continued unless there was evidence of disease progression or unacceptable toxicity. RESULTS: Twenty patients were recruited. Overall response rate was 10% (2/20) and tumor control rate was 25% (5/20). Median progression-free and median overall survival times were 1.7 and 4.6 months, respectively. The most common hematological toxicities were leucopenia (grade 4: 35%) and neutropenia (grade 4: 30%). Grade 3 febrile neutropenia and grade 3 mucositis (functional/symptomatic) each occurred in two patients (10%). One fatal bleeding occurred during this treatment, however, the relation between this event and docetaxel was unlikely. Median inpatient period during treatment was 5.4 days (range, 0-50 days). CONCLUSION: A single-agent docetaxel regimen appeared to offer an acceptable clinical profile in patients with platinum-refractory SCCHN.     

Docetaxel and irinotecan in recurrent or metastatic head and neck cancer

BACKGROUND:

Docetaxel and irinotecan have single‐agent antitumor activity in squamous cell carcinoma of the head and neck (SCCHN). The authors sought to evaluate their combination in the treatment of patients with recurrent or metastatic SCCHN.

METHODS:

Eligibility criteria included recurrent or metastatic SCCHN with measurable disease, good performance status, and adequate laboratory parameters. Patients received docetaxel 35 mg/m² and irinotecan 60 mg/m², intravenously, on Days 1 and 8, every 21 days, until disease progression. The authors assessed UGT1A1 genotype, vascular endothelial growth factor (VEGF) in serum, and cyclooxygenase‐2 and VEGF in baseline tumor tissue.

RESULTS:

Fifty‐two patients were analyzable: 20 chemotherapy naive (Group A) and 32 previously treated with 1 chemotherapy regimen (Group B); 73% of patients had distant metastasis, and 60% were paclitaxel‐exposed. In Group A, 3 (15%) patients achieved a partial response; in Group B, 1 (3%) patient achieved a partial response. Median progression‐free survival (PFS) and overall survival were 3.3 and 8.2 months in Group A and 1.9 and 5.0 months in Group B, respectively. Common serious toxicities were diarrhea, fatigue, and anorexia. Patients with high serum VEGF had a median PFS of 2.8 months versus 1.7 months for patients with low VEGF (P = .085).

CONCLUSIONS:

Docetaxel and irinotecan had acceptable toxicities, but efficacy results in unselected patients with recurrent or metastatic SCCHN did not suggest an advantage over docetaxel alone or platinum‐based regimens. Cancer 2009. © 2009 American Cancer Society.     

Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and 5-fluorouracil (PPF) as induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Seventy patients with previously untreated stage III-IV SCCHN were included in this phase II trial. Induction treatment consisted of a maximum of three outpatient courses of paclitaxel 175 mg/m(2) as a 3-h infusion on day 1, cisplatin 100 mg/m(2) on day 2, and 5-fluorouracil (5-FU) 500-750 mg/m(2)/day as a 24-h continuous infusion on days 2-6, repeated every 3 weeks. The 5-FU dose was reduced from 750 mg/m(2)/day to 500 mg/m(2)/day due to the excessive toxicity observed in the first 14 patients enrolled. Local treatment consisted of radiotherapy and/or surgery. RESULTS: Two-hundred-and-one cycles were administered to 70 patients. The main toxicities of PPF were neutropenia (grade 4, 14%; febrile neutropenia, 4%), peripheral neuropathy (grade 2-3, 14%) and catheter-associated venous thrombosis (7%). There were three early deaths (two from neutropenic sepsis and one from pulmonary embolism), and 13 patients required hospitalization due to toxicity. Other side effects included mucositis, anorexia, diarrhea, myalgias and alopecia. The overall response rate to PPF was 88%, including 59% complete responses (CR) and 29% partial responses. The CR rates at the primary tumor and neck lymph nodes were 74% and 62%, respectively. With a median follow-up of 51 months (range 40-63 months), the estimated 5-year time-to-disease progression and overall survival rates were 56% and 44%, respectively. CONCLUSIONS: The PPF regimen has major antitumor activity and is associated with manageable toxicity as induction treatment in SCCHN patients. The high complete response rate and favorable long-term outcome justify further evaluation of this chemotherapy combination.     

Biweekly paclitaxel and cisplatin in patients with advanced head and neck carcinoma

Background: Cisplatin is an active drug in head and neck cancer. Paclitaxel seems a promising drug. This article reports a phase II assessment of the combination of the two.Patients and methods: Twenty-three patients were treated with paclitaxel 90 mg/m² over three hours plus cisplatin 60 mg/m² every other week. Sixteen patients had locoregional disease and seven had metastatic disease. None of the patients had previously been treated with chemotherapy. Nine patients had had radiotherapy to the target lesions.Results: One patient was not evaluable for response. Partial responses were observed in 32% of evaluable patients. Toxicity included asthenia (56%), neutropenia, peripheral neuropathy, anemia and vomiting.Conclusions: The overall response rate observed in this study does not seem to justify the use of this chemotherapy regimen in the palliative setting.     

Management and palliative chemotherapy for metastatic or recurrent squamous cell carcinoma of the head and neck

Squamous cell carcinoma of the head and neck with distant metastases or locoregional relapse not amenable to radical surgery or radiation therapy are incurable. Median overall survival is approximately 10 months and the site of relapse, frequently in the head and neck area, is responsible for important local and regional complications that significantly impact quality of life. This article will focus on the general management and treatment of these recurrent and/or metastatic patients. We will discuss the challenges faced by the clinician when diagnosing tumor recurrence, as well as the indications and the limitations of the locoregional and systemic treatments available to treat this population.     

Paclitaxel, cisplatin, leucovorin, and continuous infusion fluorouracil followed by concomitant chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck

The primary objective of this phase II study was to access the complete response (CR) rate to a new innovative induction regimen in patients with locally advanced head and neck cancer (LA-HNC). From October 2000 until October 2003 a total of 38 eligible patients (33 men and 5 women) entered the study. The large majority of them presented with a performance status of 0–1 and with clinical stage IV disease. Treatment consisted of three cycles of induction chemotherapy (IC) with paclitaxel 175 mg/m² in a 3-h infusion on d 1, leucovorin (LV) 200 mg/m² over 20 min immediately followed by FU 400 mg/m² bolus and then 600 mg/m² as a 24-h continuous infusion on d 1 and 2 and a cisplatin 75 mg/m² over 1-h infusion on d 2 every 3 wk. This was then followed by radiation (70 Gy) and weekly cisplatin 40 mg/m². After the completion of IC, 6/38 (16%) patients had CR. The CR rate was increased to 66% post-concomitant chemoradiotherapy (CCRT). Neutropenia (37.5%), pain (62%), nausea/vomiting (21%), and alopecia (79%) were the most frequent side effects during IC. The most pronounced toxicities during chemoradiotherapy were stomatitis (62.5%) and xerostomia (53%). Median time to progression was 11.0 mo and median survival 16.7 mo. One- and 2-yr survival rates were 73% and 38%, respectively. In conclusion, this novel induction regimen is active, is well tolerated, and can be successfully followed by CCRT with weekly cisplatin. CCRT should remain standard treatment for patients with LA-HNC. Novel induction combinations, such as that reported in the present study, should be evaluated in combination with CCRT only in the context of clinical trials.     

Weekly cisplatin paclitaxel and continuous infusion fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma: a phase II study

Background Cisplatin, paclitaxel and 5-fluorouracil (5-FU) have demonstrated significant activity in patients with advanced squamous head and neck cancer (HNSCC) despite relevant toxicity. A weekly administration of cisplatin and paclitaxel with continuous infusion of 5-FU could offer a better toxicity profile without affecting dose intensity or treatment outcome. We evaluated the toxicity and the activity of weekly cisplatin/paclitaxel with continuous infusion 5-FU in patients with recurrent and/or metastatic HNSCC.Methods A total of 44 patients were studied. Treatment consisted of two 6-week cycles with weekly cisplatin 20 mg/m² and paclitaxel 60 mg/m² and daily continuous infusion 5-FU 200 mg/m² from day 1 to 42. Patients were evaluated for toxicity and response.Results 40 out of 44 patients were evaluable for response. After two cycles we observed seven complete responses (16%) and 12 partial responses (27%), with a 43% (95% CI 28–58%) overall response rate. Stable disease was seen in 13 patients (29%) and progressive disease in 12 patients (27%). Toxicity was mild in treated patients: we observed less than 10% of grade 3/4 hematological and gastroenteric toxicity.Conclusions A weekly schedule of cisplatin and paclitaxel associated with continuous infusion 5-FU showed low toxicity in the treatment of advanced HNSCC while significant activity was conserved.     

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck

Background: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck.Patients and methods: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks.Results: Twenty-four patients with a median age of 59 years (range 42–74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%–42%). The main toxicity was hematological: neutropenia grade 3–4 in 28% of the cycles and thrombocytopenia grade 3–4 in 16%. The most significant non-hematological toxicity was asthenia grade 2–3 in 24% of the cycles.Conclusions: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.     

Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck

Background:Results with docetaxel as single drug in squamous-cellhead and neck cancer have been encouraging. The purpose of the present phaseII study is to evaluate the antitumour efficacy and toxicity of thecombination of docetaxel and cisplatin in patients with recurrent ordisseminated squamous-cell carcinoma of the head and neck (SCCHN) for whom nocurative therapy is available. Patients and methods:Eligibility criteria included: writteninformed consent; WHO performance status 2; age 18–70 years;adequate bone marrow, liver, and renal function; measurable or evaluabledisease; no previous systemic chemotherapy (prior radiotherapy and/or surgerywere allowed); no other previous or concurrent malignancy; no peripheralneuropathy. Treatment consisted of docetaxel 75 mg/m² in a one-hourinfusion after pre-treatment with prednisolone, followed by cisplatin 75mg/m² in a half-hour infusion preceded and followed by hydration.Treatment was repeated every three weeks for a maximum of eight cycles. Results:Twenty-five patients (median age 52 years, range33–66) entered the trial, all were evaluable for survival, twenty-fourfor response and toxicity. Twenty-four patients had undergone priorradiotherapy and seventeen had also had surgery. Nineteen had local-regionalrecurrence only, three had local-regional disease and distant metastases, andthree had distant metastases only. Patients received a median of 5 treatmentcycles (range 2–8). Overall response rate was 33% (8 of 24) ofpatients; complete response rate was 8% (2 of 24) of patients, lasting2.2 and 17.1 months, respectively; partial response rate was 25% (6 of24) of patients, lasting for a median of 4.9 months (range 1.7–11.6months). Median survival was 11 months. Toxicity was relatively welltolerated. However, one patient died of probable toxicity (neutropenia andinfection) and three patients discontinued treatment because of toxicity(massive oedema, myocardial infarction, persistent thrombocytopenia). The mostfrequent moderate-to-severe toxicity (75% of patients) was grade3–4 neutropenia, transient in all but one patient. Grade 3 neuropathyoccurred in one patient, none had grade 4. Grade 3 oral mucositis occurred inthree patients, none had grade 4. Grade 2–3 hypomagnesaemia occurred in10 patients requiring magnesium infusion. Conclusions:Docetaxel and cisplatin is an active combination inpatients with recurrent or disseminated SCCHN. Remissions are however fairlyshort. Toxicity is significant, but generally manageable.     

Docetaxel in the management of patients with head and neck squamous cell carcinoma

The taxanes play a significant role in the treatment of various solid tumors of epithelial origin. Docetaxel is the most extensively studied taxane in prospective head and neck cancer trials and has been investigated as induction chemotherapy or in combination with radiotherapy in locally advanced squamous cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or metastatic disease. The data in locally advanced disease are particularly compelling. Three recently reported randomized trials, carried out in patients with locally advanced disease who were receiving induction chemotherapy followed by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the standard induction regimen of cisplatin/5-fluorouracil (PF) significantly improved survival compared with PF alone, without significantly increasing toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current standard induction regimen and TPF-based sequential therapy can be considered a standard treatment alternative to chemoradiotherapy alone in patients with locally advanced HNSCC. This review article discusses the current developments of docetaxel-based chemotherapy and the optimal use of this agent in patients with HNSCC.     

Efficacy of intra-arterial infusion therapy using a combination of cisplatin and docetaxel for recurrent head and neck cancers compared with cisplatin alone

Aims: To compare the initial effect and toxicity, response duration and survival time of intra-arterial infusion therapy using a combination of cisplatin (CDDP) and docetaxel (DXT) with those using CDDP alone for treatment of recurrent head and neck cancers.Materials and methods: Twenty-nine patients with recurrent head and neck cancers were treated using intra-arterial infusion chemotherapy. The chemotherapeutic regimens consisted of CDDP alone (n=12) or a combination of CDDP and DTX (n=17). In the CDDP-DTX group, both CDDP 70 mg/m²and DTX 60 mg/m²were administrated via the external carotid artery (ECA) or via branches of the ECA or subclavian artery. In the CDDP-alone group, CDDP 70 mg/m²was infused. The tumour response (response rate = complete response + partial response) and toxicities (World Health Organization [WHO] classification grades 3 and 4) were evaluated in both groups and compared by Fisher's exact probability test.Results: The response rates in the CDDP-DTX group and the CDDP-alone group were 71% (12/17) and 50% (6/12), respectively (P=0.44). Leucocytopenia and neutropenia (grades 3 and 4) were significantly more prevalent in the former than in the latter group (11/17 vs 1/12; 10/17 vs 1/12) (P<0.01). However, there were no infectious diseases in any of the patients.Conclusion: Combined cisplatin-docetaxel intra-arterial infusion therapy was shown to be effective and safe for recurrent head and neck cancers.     

Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: Final results of a randomized, double-blind, placebo-controlled, phase 3 study

BACKGROUND:

Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum‐based chemotherapy is often a first‐line treatment. Pemetrexed has shown single‐agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed‐cisplatin for SCCHN.

METHODS:

In a double‐blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²; n = 398) or placebo plus cisplatin (75 mg/m²; n = 397) to assess overall survival (OS) and secondary endpoints.

RESULTS:

Median OS was 7.3 months in the pemetrexed‐cisplatin arm and 6.3 months in the placebo‐cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75‐1.02; P = .082). Median progression‐free survival (PFS, months) was similar in both treatment arms (pemetrexed‐cisplatin, 3.6; placebo‐cisplatin, 2.8; HR, 0.88; 95% CI, 0.76‐1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed‐cisplatin (n = 347) led to longer OS and PFS than placebo‐cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed‐cisplatin (n = 86) resulted in longer OS and PFS than placebo‐cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed‐cisplatin toxicity was consistent with studies in other tumors.

CONCLUSIONS:

Pemetrexed‐cisplatin compared with placebo‐cisplatin did not significantly improve survival for the intent‐to‐treat population. However, in a prespecified subgroup analysis, pemetrexed‐cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers. Cancer 2012. © 2012 American Cancer Society.     

Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck

BACKGROUND: Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC. METHODS: Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty-three additional patients were treated with this dose. RESULTS: Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted. CONCLUSIONS: The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial.