尼妥珠单抗联合多西他赛和顺铂一线治疗复发或转移性头颈部鳞癌疗效观察

目的 观察尼妥珠单抗联合多西他赛和顺铂一线治疗复发或转移性头颈部鳞癌的疗效及安全性.方法 回顾性分析28例尼妥珠单抗联合多西他赛+顺铂(观察组)及30例多西他赛+顺铂(对照组)一线治疗复发或转移性头颈部鳞癌患者的临床资料,比较两种方案的客观缓解率(ORR)、疾病控制率(DCR)、无进展生存时间(PFS)及总生存时间(O...     

Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study.

PURPOSE: Therapy of recurrent/metastatic squamous cell carcinoma of the head and neck results in median progression-free survival (PFS) of 2 months. These cancers are rich in epidermal growth factor receptor (EGFR). We wished to determine whether the addition of cetuximab, which inhibits activation of EGFR, would improve PFS. PATIENTS AND METHODS: Patients with recurrent/metastatic squamous cell carcinoma of the head and neck were randomly assigned to receive cisplatin every 4 weeks, with weekly cetuximab (arm A) or placebo (arm B). Tumor tissue was assayed for EGFR expression by immunohistochemistry. The primary end point was PFS. Secondary end points of interest were response rate, toxicity, overall survival, and correlation of EGFR with clinical end points. RESULTS: There were 117 analyzable patients enrolled. Median PFS was 2.7 months for arm B and 4.2 months for arm A. The hazard ratio for progression of arm A to arm B was 0.78 (95% CI, 0.54 to 1.12). Median overall survival was 8.0 months for arm B and 9.2 months for arm A (P = .21). The hazard ratio for survival by skin toxicity in cetuximab-treated patients was 0.42 (95% CI, 0.21 to 0.86). Objective response rate was 26% [corrected] for arm A and 10% [corrected] for arm B (P = .03). Enhancement of response was greater for patients with EGFR staining present in less than 80% of cells. CONCLUSION: Addition of cetuximab to cisplatin significantly improves response rate. There was a survival advantage for the development of rash. Progression-free and overall survival were not significantly improved by the addition of cetuximab in this study.     

Phase II study of vinorelbine/cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck progressing after at least two chemotherapy regimens

The aim of the present study was to identify a potentially effective new treatment regimen for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck in disease progression after at least two previous chemotherapy regimens. The "novel" regimen was Cetuximab administered weekly plus Vinorelbine on days 1, 8, 15 every 28days. The regimen was administered to patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery, radiotherapy or both and progressing after at least two chemotherapy regimens. Twenty-four patients with histologically confirmed tumors of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were stage IV and 91.6% had an ECOG PS 0-1. After 3 cycles of treatment 23 patients (95.8%) were evaluable for response: 4 patients had partial response; 12 stable disease and 7 progressive disease. Disease control rate was 69.5%. At a median follow-up of 21.3months, the median progression-free survival was 5.8months. Median duration of response was 5.2months. At May 2010, 11/24 (45.8%) patients were alive. The safety profile was quite good. The present study shows that the combination of Vinorelbine and Cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck patients is effective, feasible and has a good safety profile. Our findings warrant further investigation in a wider patient population.     

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.     

Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer

We report the results of a randomised phase II trial of docetaxel tested as a single agent in patients with recurrent head and neck cancer using methotrexate as a control arm to validate the results. Eligibility criteria included: histologically-confirmed squamous cell carcinoma, measurable disease, adequate haematological, renal and hepatic functions, no prior chemotherapy for recurrent cancer, signed informed consent. 40 mg/m2 methotrexate was given as a short weekly bolus i.v. injection, and 40 mg/m2 docetaxel was administered as a one hour weekly infusion. A total of 57 patients were randomised based on a ratio of 2/1:37 and 20 patients received docetaxel and methotrexate, respectively. Patient characteristics included 49 males and 8 females; the median age was 59 years (range: 43-82 years). Twenty-eight patients had a local-regional relapse and 29 had distant metastasis, the median disease-free interval was 7.9 months (range: 0-165 months). For patients treated with docetaxel, the following grade 3-4 toxicities occurred: neutropenia (12.5%) with febrile neutropenia in one patient (1%), anaemia (19%) mucositis (9%) and ungueal toxicity (9%). In the methotrexate arm, the grade 3-4 toxicities were: anaemia (15%) and mucositis (5%). The response rate was significantly higher in the docetaxel arm with 27% (95% confidence interval (CI): 21.7-32.3%) of objective responses versus 15% (95% CI: 11.2-18.8%) in the methotrexate arm. Overall survival and time to progression were super-imposable between the docetaxel and methotrexate treatments. Docetaxel given as a weekly infusion has a high activity in patients with head and neck cancer. A phase III trial is needed to test if this translates into a survival benefit for docetaxel use.     

Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393)

Recurrent or metastatic squamous carcinoma of the head and neck (RMSCHN) is a modestly chemoresponsive tumor; however, currently available agents have failed to improve survival. New active agents are needed for the treatment of this disease. Topotecan is a topoisomerase inhibitor that demonstrated initial promising activity in squamous carcinoma of the head and neck. The Eastern Cooperative Oncology Group conducted a phase II trial of topotecan to determine the efficacy and toxicity of a weekly treatment schedule in patients with RMSCHN. Patients with metastatic or locally recurrent squamous carcinoma of the head and neck were treated with topotecan 1.5 mg/m2 x 24 hours by continuous infusion on days 1, 8, 15, and 22 of each 35-day cycle. Patients were stratified in two cohorts: chemonaive and previously treated. Sixteen chemonaive and 16 previously treated patients were registered on study. Grade III/IV neutropenia and anemia occurred in 16% and 18% of patients, respectively. No responses were observed in either cohort. Median survival for previously untreated patients was 4.6 months and 3.2 months for previously treated patients.Topotecan failed to demonstrate efficacy in patients with RMSCHN. Further evaluation of this agent is not planned.     

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.     

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.     

Weekly paclitaxel and carboplatin combination chemotherapy in patients with advanced squamous cell carcinoma of the head and neck

BACKGROUND: The combination of paclitaxel and carboplatin is active in the treatment of squamous cell carcinoma of the head and neck (SCCHN). However, considerable toxicity develops with 3-weekly drug administration. Treatment on a weekly basis may allow for a higher dose intensity with less adverse effects. PATIENTS AND METHODS: Enrolled in this study were 31 patients with locally advanced, metastatic or relapsed SCCHN, most of them pretreated. They received weekly i.v. infusions of 80 mg/m(2) paclitaxel over 1 h combined with carboplatin at an area under the concentration time curve of 2 mg/ml/min over 30 min. RESULTS: The overall response rate was 52% with 1 complete response and 16 partial responses. Median progression-free survival was 5.4 months, median overall survival 12.8 months. Grade 3/4 hematologic adverse events occurred in 7 patients and grade 3 peripheral neuropathy in one. 10 patients required dose reduction or treatment delay due to neutropenia, thrombocytopenia or neuropathy. CONCLUSIONS: Weekly administration of paclitaxel and carboplatin appears to be safe and efficacious in patients with advanced, metastatic or recurrent SCCHN.     

Palliative weekly chemotherapy along with cetuximab in recurrent and metastatic head and neck cancers: A retrospective analysis

Background: This study was undertaken to report the results of weekly combination chemotherapy with cetuximab in recurrent/metastatic head and neck squamous cell carcinoma (R/M SCCHN). Materials and Methods: Retrospective analysis of 35 R/M SCCHN patients who received cetuximab with weekly paclitaxel and platin (cisplatin/carboplatin) from SCCHN August 2006 to October 2008 at our Institute was performed. Results: Thirty-five patients (33 [94.3%] males and 2 [5.7%] females) received the planned weekly chemotherapy protocol. Median age of these patients was 52 years. Of the SCCHN 32 evaluable patients, 25 patients showed symptomatic improvement and 7 showed no improvement. Radiological responses using RECIST criteria reported CR in 1 patient (3.1%), PR in 17 patients (53.1%), and SD in 6 patients (18.8%). The remaining six patients demonstrated disease progression while two could not be assessed. Median overall survival (OS) was 8.016 months (95% CI; 6.572--9.461) and median PFS was 5.782 months (95% CI; 4.521--7.044). The major chemotherapy-related grades 2 and 3 toxicity recorded was cetuximab-induced rash reported in 24 patients. No treatment-related death within 30 days was observed. Conclusion: Cetuximab with weekly combination chemotherapy (Paclitaxel + Platinum compound) has shown promise, demonstrating comparable response and outcomes with acceptable toxicity in R/M SCCHN patients.     

Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study

Carboplatin/docetaxel chemotherapy was evaluated in advanced squamous cell carcinoma of the head and neck (SCCHN). Eligibility included patients with recurrent, persistent, or metastatic SCCHN with Zubrod performance status 0-2. Docetaxel 65 mg/m² and carboplatin (AUC of 6) were given IV in a 21-day cycle to 68 patients. Response probability was 25 percent (95%CI: 15-38). The major toxicity observed was neutropenia, with 36 patients (61 percent) experiencing Grade 3 or worse. Median progression-free survival was 3.8 months (95%CI, 3.1-4.8) Median overall survival was 7.4 months (95%CI, 6.2-8.9). The results of this study suggest this regimen is active for outpatient treatment of recurrent SCCHN patients with good performance status.     

Phase II study of methotrexate,vinblastine, doxorubicin,and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck

BACKGROUND: The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population. METHODS: Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4-week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival. RESULTS: Thirty-six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33-60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1-year progression free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21-63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1-year progression free survival rate was 23% (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate was 54% (95% CI, 33-89%). CONCLUSIONS: Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck.     

Cetuximab in the treatment of squamous cell carcinoma of the head and neck

The majority of the head and neck cancers are squamous cell carcinomas, which commonly overexpress the EGF receptor (EGFR). Cetuximab is a chimeric monoclonal antibody that binds with high affinity to the extracellular domain of EGFR, and in addition induces antibody-dependent cellular cytoxicity. In a randomized Phase III trial in patients with locoregionally advanced squamous cell carcinoma of the head and neck, the addition of cetuximab to radiotherapy prolonged the median time of locoregional control from 14.9 to 24.4 months and increased the median overall survival from 29.3 to 49.0 months. In patients with platinum-refractory recurrent and/or metastatic disease, the objective response and disease-control rates in various studies ranged from 10 to 13% and from 46 to 56%, respectively. In the EXTREME trial, the addition of cetuximab to platinum/5-fluorouracil as first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck not only led to significant improvements in survival, response rate and disease control, but also induced a better symptom control in comparison with that observed with platinum/5-fluorouracil alone.     

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck

OBJECTIVE: Twenty-seven patients with recurrent squamous cell carcinoma of the head and neck were entered in a multicenter study to determine the efficacy of the paclitaxel-carboplatin association. METHODS: Standard eligibility criteria applied, i.e. measurable disease, and chemotherapy given as induction treatment or concomitant chemoradiotherapy was allowed if completed more than 6 months prior to the study. Every 21 days, paclitaxel 175 mg/m(2) and carboplatin AUC 6 were administered. The patient group included 3 females and 24 males with a median age of 61 years (range 39-75 years). RESULTS: All patients were assessable for toxicity and 24 for responses. Main grade 3-4 toxicities were: neutropenia (62.9%), febrile neutropenia (18.5%), anemia (11.1%), thrombocytopenia (14.8%), mucositis (7.4%) and vomiting (7.4%). Among the intent-to-treat population, 29.6% of patients had an objective response, with a median response duration of 4.2 months (range 1-5.7 months). Stable and progressive disease were observed in 11.1 and 48.1% of patients, respectively. The median overall survival was 7.2 months (range 0.5-10.9 months). CONCLUSION: From these data, paclitaxel-carboplatin seems to have an activity in recurrent squamous cell carcinoma of the head and neck, but the high level of toxicity highlights the need to search for a safer chemotherapy combination.     

Larynx-sparing radiotherapy for squamous cell carcinoma from an unknown head and neck primary site

The objective of this study was to evaluate the efficacy of larynx-sparing radiotherapy (RT) alone or in combination with a neck dissection for patients with squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck primary site. Seventeen patients were treated with curative intent between 1997 and 2002; 16 of 17 patients had follow up for at least 2 years. No patient developed a squamous cell carcinoma in a head and neck mucosal site after treatment. One patient (6%) had persistent nodal disease and 1 patient (6%) had recurrent nodal disease 1 year after completing RT. No patients experienced distant metastases. The 5-year cause-specific and overall survival rates were 88% and 82%, respectively. Based on our limited experience, larynx-sparing RT appears to result in a high likelihood of local-regional control and survival and likely reduces both acute and late toxicity.     

Chemotherapy for head and neck cancer. Comparison of cisplatin + vinblastine + bleomycin versus methotrexate

One hundred ninety-one patients with recurrent or metastatic squamous cell carcinoma of head and neck origin were allocated at random to chemotherapy with conventional-dose weekly intravenous methotrexate or the combination of cisplatin, vinblastine, and bleomycin. Methotrexate induced responses in 16 of 98 patients (16%), whereas 22 of 92 (24%) responded to the combination regimen (P = not significant). Remission duration (20.2 weeks methotrexate; 15.1 weeks combination) was similar on both arms, as was survival (31.4 weeks methotrexate; 29.0 weeks combination). Therapy was relatively well-tolerated on both treatment arms, although methotrexate produced more mucositis and the combination more gastrointestinal and renal toxicity. Response to chemotherapy and disease confined to the locoregional area were associated with somewhat longer survival. Combination chemotherapy as given in this study did not improve any observed parameter, and the results of treatment were poor in both arms.     

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.     

Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy.

PURPOSE: To evaluate the outcome of elderly patients with head and neck cancer undergoing palliative chemotherapy. PATIENTS AND METHODS: We analyzed combined data from two mature phase III randomized trials conducted by the Eastern Cooperative Oncology Group (ECOG; trial E1393, which compared cisplatin plus paclitaxel at two dose levels, and trial E1395, which compared cisplatin plus fluorouracil to cisplatin plus paclitaxel) to evaluate the toxicity, objective response rates, and survival of patients 70 years or older versus their younger counterparts. All patients had previously untreated recurrent or metastatic squamous cell carcinoma of the head and neck and ECOG performance status 0 or 1. RESULTS: Fifty-three elderly patients were enrolled from a total of 399 eligible participants (13%). Elderly patients had similar objective response rates (28% v 33%) and median time to progression (5.25 v 4.8 months) compared with younger patients. The median survival was 5.3 v 8 months (Wilcoxon P =.06; log-rank P =.17) and the 1-year survival 26% v 33% for elderly and younger patients, respectively. Elderly patients had a significantly higher incidence of severe nephrotoxicity, diarrhea, and thrombocytopenia. A higher rate of toxic deaths was noted in the elderly but did not reach statistical significance (13% v 8%; P =.29). CONCLUSION: Elderly patients were underrepresented in these studies. Fit elderly patients with recurrent or metastatic head and neck cancer sustained increased toxicities with cisplatin-based doublets but had comparable survival outcomes compared with younger patients. Strategies to ameliorate toxicities should be pursued in the elderly.     

A prospective randomized trial of methotrexate versus cisplatin in the treatment of recurrent squamous cell carcinoma of the head and neck

A prospective randomized study was conducted to determine the relative effectiveness, toxicity and tolerance of methotrexate (MTX) versus cisplatin (DDP) in patients with recurrent head and neck squamous cell carcinoma. Forty-four patients were randomized to receive either MTX, 40 mg escalated to 60 mg/m2 IV push weekly, or DDP, 50 mg/m2 6 hour infusion days 1 and 8 every 4 weeks. All patients had objectively measurable disease and a performance status greater than 60% (Karnofsky scale). All had been treated with surgery and/or radiotherapy. No patients had prior chemotherapy. Prior treatment, performance status, and site of primary disease were comparable in both groups. Complete and partial objective responses were achieved in 23.5% of the MTX group and 28.6% of the DDP group (P = 0.51). Median duration of response was 84 days in the MTX group and 92 days in the DDP group. Median survival of patients was 6.1 months with MTX and 6.3 months with DDP. Mucositis was noted in 38% of patients in the MTX group (P = 0.001) compared to none in the DDP group. Vomiting occurred in 87% of patients in the DDP group (P less than .0001) compared to 10% of patients in the MTX group. This study demonstrates that in the treatment of recurrent head and neck squamous cell carcinoma, MTX and DDP are equally effective, although MTX appears to be better tolerated.     

Paclitaxel and gemcitabine in advanced non-nasopharyngeal head and neck cancer: A phase II study conducted by the Hellenic Cooperative Oncology Group

Background: Paclitaxel as monotherapy or in combination with other drugs has demonstrated significant activity in patients with squamous cell carcinoma of the head and neck region (SCCHN). Preclinical studies have shown gemcitabine to be highly active in SCCHN cell lines.Purpose of the study: To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and gemcitabine as first-line chemotherapy in patients with recurrent and/or metastatic head and neck cancer (HNC).Patients and methods: From September 1996 until May 1998, 44 patients with non-nasopharyngeal recurrent and/or metastatic HNC entered the study. There were 37 men and seven women with a median age of 61 years (range 35–79) and a median performance status of 1 (range 0–2). The location of the primary tumor in the majority of them was either the larynx or the oral cavity. Treatment consisted of six cycles of gemcitabine 1100 mg/m2 over 30 min on days 1 and 8 immediately followed on day 1 by paclitaxel 200 mg/m2 by three-hour infusion. The treatment was repeated every three weeks.Results: Twenty-four (55%) patients completed all six cycles of treatment. A total of 205 cycles were administered, 165 (81%) of them at full dose. The median relative dose intensity (DI) of gemcitabine was 0.93 and of paclitaxel 0.95. Except for alopecia, which was universal, grade 3–4 toxicities included neutropenia (21%), thrombocytopenia (5%), anemia (5%), infection (5%), flu-like syndrome (5%) and peripheral neuropathy (2%). Five (11%) patients achieved complete and 13 (30%) partial responses, for an overall response rate of 41%. After a median follow-up of 13 months, the median time to progression was four months and median survival nine months.Conclusions: The combination of paclitaxel and gemcitabine is active and well tolerated in patients with recurrent and/or metastatic HNC – randomized studies comparing this combination with other regimens are warranted.