Combined Chemotherapy for Recurrent and Metastatic Nasopharyngeal Carcinoma

Summary

Thirty-two patients (24 males, 8 females; median age 54 yrs) with recurrent and/or metastatic undifferentiated carcinoma of the nasopharyngeal type were treated with chemotherapy. Remissions were observed in 17 of 32 (53.2%) with 5 complete (CR) (15.6%) and 12 partial responses (PR) (37.6%). A combination of cisplatin and 5-fluorouracil was the most effective regimen (CR + PR = 83.3%). Objective responses. (CR + PR) were 47% (CR=11.7%) in schemes without cisplatin and 60% (CR = 20%) in cisplatin-based combinations. The median overall duration of response was 7.2 months. The median overall survival time was 10.3 months: 15.1 months for responders and 5.2 for non-responders. No important toxicity was observed.     

Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer

In this phase II multicenter trial, 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). The overall response rate was 64%, including 21% complete responses (CRs). In 55 patients with metastatic disease, 31 responses (51%) including eight CRs (15%) were achieved. Responses were seen in all metastatic sites, but the response rate was lower in patients with peritoneal carcinomatosis. In 12 patients with locoregional disease, six CRs and six partial responses (PRs) were observed. Eight CRs (three and five in patients with metastatic and locoregional disease, respectively) were pathologically confirmed. The overall median response duration was 7 months; it was 16 months for patients achieving CR (22 months for pathologically confirmed CR [pCR]), and 6 months for PR. The median survival time for all patients was 9 months, for the patients who achieved CR 17 months, for pCR 23 months, and for PR 9.5 months. Median survival time for all patients with metastatic disease was 8 months, and for locoregional disease 12.5 months. Six patients (9%) (four local, two metastatic disease) were alive at 2 years, and four patients are alive and disease free at 35+ to 56+ months. Main toxicities were leukopenia and thrombocytopenia, with 64% of patients developing grade 3 to 4 myelosuppression and 12% severe infections. Nonhematologic toxicities of World Health Organization (WHO) grade 4 were not observed.     

Phase II study with docetaxel and cisplatin in the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck

PURPOSE: Since the combination of cisplatin and docetaxel have demonstrated activity in squamous cell carcinomas of the lung and oesophagus before, promising results in recurrent metastatic head and neck cancer were expected. PATIENTS AND METHODS: Between September 1998 and October 2000, 40 patients entered this trial, 38 of whom were evaluable. Six patients were previously untreated, 24 had surgery and/or radiotherapy and 13 had received chemoradiation and/or surgery. Therapy consisted of 75 mg/m(2) docetaxel (1-hour infusion) and 75 mg/m(2) cisplatin (90-min infusion) on day 1, repeated every three weeks for a maximum of 6 courses. All patients received corticosteroids routinely, 5-HT3-antagonists, and hydration. RESULTS: The overall response rate was 52.5% (95% confidence interval, 36.1 to 68.5%) including 7 complete (17.5% complete response; CR) and 14 partial remissions (35% partial response; PR). The overall response rate in patients who had no prior treatment (n = 6) was 100%, including 3 CR and 3 PR. In patients who had prior surgery and/or radiotherapy (n = 21) an overall response rate of 42.8% was observed, including 2 CR and 7 PR; 8 patients (38.1%) had stable disease, while disease progressed in 3 (14.3%). Six of 13 patients (46.2%) who had prior chemoradiation +/- surgery responded, including 2 CR (15.4%) and 4 PR (30.8%), no change was seen in 4 patients (30.8%) and tumour progressed in 2 (15.4%). The median response duration for all patients was 10 months (range, 3-20), the median overall survival was 11 months (range, 1-30). Myelosuppression was commonly observed; WHO grade 3 or 4 neutropenia occurred in 12 patients (30%) each, and was complicated by septicaemia in 5 cases. WHO grade 3 anaemia was observed in only 3 patients (7.5%). Severe non-hematologic toxicity except for alopecia was rarely observed, and included diarrhea in 2 (5%), nausea/vomiting in 2 patients (5%) and stomatitis in 1 patient (2.5%). CONCLUSION: Our data suggest that docetaxel and cisplatin in combination is an effective and fairly well tolerated regimen for the treatment of head and neck cancer with an excellent response rate in previously untreated patients.     

Combination chemotherapy with cisplatin, ifosfamide and adriamycin in patients with advanced transitional cell carcinoma of the urinary tract

A combined chemotherapy with cisplatin, ifosfamide and adriamycin (CIA therapy) was performed in 20 patients with advanced transitional cell carcinoma of the urinary tract. Adriamycin 30mg/m2 and ifosfamide 1.5g/m2 were administered on day 1 and cisplatin 50 mg/m2 on day 2, which was repeated at intervals of 3 weeks, in principle. According to Koyama and Saito's response criteria, complete response (CR), partial response (PR) and minor response (MR) were obtained in 1, 4 and 5 cases, respectively; CR+PR+MR in 10 cases out of 18 evaluable cases (56%). The duration of response was 2 to 14 months (median; 4 months) in the cases with CR and PR. The survival time of the responders ranged from 3 to 23 months (median; 11 months), being significantly longer than that of the non-responders (p less than 0.05, Generalized Wilcoxon test). Adverse reactions observed were of a slight or moderate degree, with only a few cases of damage to renal function.     

Cisplatin, bleomycin, and methotrexate (PBM) chemotherapy in locally advanced and metastatic head and neck cancer

Twenty-two patients with locally advanced or metastatic head and neck tumors received a total of 84 courses of a combination of cisplatin, bleomycin, and Methotrexate (PBM) for a median of four courses per patient (range, 1-7). Among these 22 patients there were four patients (18%) who achieved complete remission (CR) and 13 patients (60%) who had a partial remission (PR). The overall remission rate (CR + PR) thus reached 78%; five patients (22%) progressed while on therapy. The mean duration of objective response (CR + PR) was 8 months; CR lasted a median of 18 months (range, 2-48). Survival was not influenced by tumor histology or by previous surgery. The presence of locoregional disease did adversely affect survival from the onset of chemotherapy (P = 0.1). The rate of survival was also affected by primary tumor site; patients with nasopharyngeal primaries survived longer than all other patients (22 vs. 11 months, P = 0.06). Toxicity to chemotherapy consisted mainly of nausea and vomiting and stomatitis. Three patients developed fever while leukopenic. One patient experienced irreversible renal damage, and another suffered from bleomycin-induced pulmonary fibrosis. The high response rate obtained in our group of patients did not have a substantial impact on overall survival. Aggressive, multimodality approaches should be considered in the treatment of these patients when possible.     

Treatment of metastatic malignant melanoma with 24 hours continuous venous infusion of dacarbazine and cisplatin

Twenty consecutive patients with metastatic malignant melanoma were treated with a combination of 24 hours continuous infusion of dacarbazine (250 mg/m2) and cisplatin (20 mg/m2) for 5 days every 3 weeks. One patient (5%) achieved a complete response (CR) and 3 patients (15%) obtained a partial response (PR) with an overall response rate of 20%. Minimal response was observed in 5 other patients (25%). Complete response duration was 8 months. Median response duration of partial responders was 7 months. Median survival of all responders (CR+PR) was 8.5 months. Toxicity was mild to moderate.     

A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro-Oncologia

BACKGROUND: No data on the role of chemotherapy in recurrent ependymal tumors are available in adults. The aim of the current study was to investigate outcomes after salvage chemotherapy in this setting. METHODS: A retrospective review was made of the charts of 28 adults (> or = 18 years) with progressive or recurrent ependymal tumors after surgery and radiotherapy, who received chemotherapy between 1993 and 2003 in 3 institutions of the Gruppo Italiano Cooperativo di Neuro-Oncologia network. RESULTS: Thirteen patients (46.3%) received cisplatin-based chemotherapy (Group A) and 15 (53.7%) received regimens without cisplatin (Group B). Platinum-based chemotherapy yielded 2 complete responses (CR) (15.4%) and 2 (15.4%) partial responses (PR), whereas 7 patients (53.8%) remained stable (SD). After regimens without cisplatin, there were no CR, 2 PR (13.3%), and 11 SD (73.3%). The overall median time to progression was 9.9 months (95% confidence interval [95% CI], 7.5-21.7 months), 9.9 months (5.2-not reached) for Group A and 10.9 months (95% CI, 7.17-23.9 months) for Group B. The overall median survival (OS) was 40.7 months (95% CI, 16-not reached), 31 months (21-not reached) for Group A and 40.7 months (13.4-not reached) for Group B. CONCLUSIONS: Cisplatin-based chemotherapy achieved a higher response rate, but did not prolong disease progression-free survival or OS. More active regimens for the salvage treatment of ependymal tumors have yet to be found.     

Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University

The role of chemotherapy in the management of patients with cancer of the paranasal sinus has not been defined. An analysis of 24 evaluable patients treated with chemotherapy as part of their overall therapy was performed. There were 16 male patients and eight female patients. Sixteen patients were previously untreated and eight had recurrent disease after surgery and/or radiotherapy. Six of the previously untreated patients had metastatic disease on presentation (four central nervous system (CNS) and two lung), and four recurrent patients had CNS involvement. The majority of patients (78%) had squamous cell carcinoma. The chemotherapy regimens included cisplatin (CDDP), vincristine (VCR), and bleomycin (COB), 5-fluorouracil (5-FU) infusion and CDDP, or 5-FU/CDDP and methotrexate (MTX). All patients had computed tomography (CT) measurable disease. Previously untreated patients underwent surgery and/or radiotherapy postchemotherapy. The overall response rate to chemotherapy for previously untreated patients was 82% (complete response [CR] 44%, partial response [PR] 38%) and for recurrent patients 88% (CR 38%, PR 50%). Predominant toxicities were nausea, vomiting, myelosuppression, mucositis, and renal impairment. The median survival of the previously untreated patients, based on response to chemotherapy, was as follows: CR 21+ months (range, 10+ to 81 months), PR 13.5 months (range, 2 to 21 months), and no response (NR) 3 months (range, 1 to 7 months). The median survival of patients with recurrent disease was as follows: CR 16 months, PR 13.5 months, and NR 5 months. We conclude that patients with paranasal cancers are responsive to CDDP-containing combinations. The role of adjuvant chemotherapy in previously untreated, locally advanced patients needs to be demonstrated by future randomized trials.     

Results of a combined chemo-radiotherapeutic program in 61 patients affected by small cell lung cancer

Sixty-one patients affected by small cell lung cancer (SCLC) entered in the study. Eighteen had limited disease and 43 extensive disease. Treatment consisted of: induction chemotherapy with 3 courses of CAV (cyclophosphamide, adriamycin, vincristine) in limited disease patients or 2 courses of CAV plus 2 courses of DDP-VP16 (cisplatin, etoposide) in extensive disease patients, followed by chest radiotherapy and CNS prophylaxis in responsive patients. Subsequently, responders and stable patients received maintenance chemotherapy by the alternation of cycles of CAV, DDP-VP16 and C'MP (CCNU, methotrexate, procarbazine), which lasted 1 year or until relapse. Four of 17 limited disease patients (23%) obtained a CR and 11 (65%) a PR; their median survival was 11 months (range, 2+-36+). One of the 7 extensive disease patients (3%) achieved a CR and 19 (51%) a PR; their median survival was 6 months (range, 1-22). Median duration of response was 12 months for CR and 5 months for PR. Responders (CR and PR) survived 11.5 months versus 3.5 months for failures (P less than 0.05); 3/61 (5%) showed long-term survival, in the absence of disease. The overall median survival was 7 months (range, 1-36+). The main toxic effects were myelosuppression and vomiting (WHO grade 3). From our results, this program does not offer further substantial gains in patients with SCLC.     

High-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma

A chemotherapy regimen with epirubicin (60 mg/m2, days 1, 2 and 3) and cisplatin (30 mg/m2, days 2, 3, 4 and 5) was started for 35 patients with advanced soft tissue sarcoma (28 males and 7 females; median age, 50 years). All patients were chemotherapy-naive and with an expected survival of more than 2 months. All patients were evaluable for activity and toxicity. The intercycle interval was 4 weeks. Median number of cycles applied was 4 (range, 2-8). The overall response rate was 20/35 (57.1%). A complete response (CR) was achieved in 7/35 patients (20%), lasting for 26+, 26+, 13+, 13+, 9+, 9+ and 5 months; 13/35 patients (37.1%) entered a partial remission (PR), 9/35 patients (25.7%) had stable disease (SD), and 6/35 (17.1%) had progressive disease (PD). In non-responders (SD + PD), the median survival was 4 months; the median survival of responders (CR + PR) was 9+ months (the median has not yet been reached). Hematologic toxicity of grade 4 was present at least in one cycle for hemoglobin in 6/35 patients, for leukocytes in 22/35, and for platelets in 13/35. No hemorrhagic syndrome was observed. The leukopenia was usually of short duration (nadir on days 10-12). Febrile episodes were present in 18 patients during the nadir of leukopenia. No other significant toxicity was noted (apart from grade III alopecia in all patients), and specifically, there was neither acute nor cumulative cardiotoxicity.     

Randomized comparison of cisplatin plus epirubicin or doxorubicin for advanced epithelial ovarian carcinoma. A multicenter trial.

Stage III and IV epithelial ovarian cancer patients were prospectively randomized to receive eight courses of 60 mg/m2 of cisplatin plus either 75 mg/m2 of epirubicin (62 patients) or 60 mg/m2 of doxorubicin (54 patients). Clinical response rates for cisplatin/epirubicin of 42% [15% complete response (CR) and 27% partial response (PR)] and for cisplatin/doxorubicin of 55% (24% CR and 31% PR) were not statistically different (p = 0.14). The negative second look rate was 35% (10/29) for cisplatin/doxorubicin and 17% (5/30) for cisplatin/epirubicin (p = 0.12). The progression-free interval for cisplatin/epirubicin (13 months) was not statistically different (p = 0.09) from that for cisplatin/doxorubicin (19 months). The median survivals for cisplatin/epirubicin (756 days) and cisplatin/doxorubicin (739 days) were similar (p = 0.70). Cardiotoxicity was greater for the cisplatin/doxorubicin group (p = 0.0003). With similar survival and less cardiotoxicity, the cisplatin/epirubicin regimen had the more favorable therapeutic index.     

GP和FP治疗转移性鼻咽癌的疗效观察

目的：观察吉西他滨＋顺铂（GP）方案和氟尿嘧啶＋顺铂（FP）方案治疗晚期复发转移性鼻咽癌的疗效及不良反应。方法：选择放疗后复发转移性鼻咽癌60例,分别采用GP方案或FP方案静脉化疗,21天为1周期。结果：GP组：CR5例、PR19例,有效率（CR＋PR）80％;FP组：CR2例、PR14例,有效率（CR＋PR）53．3％两组有效率有显著差异（P=0．0283）。中位PFS（无进展生存期）GP组8个月,FP组3个月（P=0．0001）。中位OS期（总生存期）GP组11个月,FP组7个月（P=0．0002）。两组毒性均能耐受。结论：GP方案较FP可以更好改善复发转移性鼻咽癌的RR、PFS和OS。     

Cisplatin, epirubicin and 5-fluorouracil combination chemotherapy for recurrent carcinoma of the salivary gland

Nine patients (5 males, 4 females; median age, 62 years) with recurrent high-grade malignancies of major (7 cases) and minor (2 cases) salivary gland origin (4 adenoid cystic carcinomas, 2 adenocarcinomas, 2 poorly differentiated carcinomas, 1 mixed malignant tumor) were treated with cisplatin (60 mg/m2), epirubicin (50 mg/m2) and 5-fluorouracil (600 mg/m2) (CEF) by intravenous injections on the first day of a 21-day regimen. Previous therapy included surgery (1 case), radiotherapy (1 case), and surgery + radiotherapy (7 cases). There was 1 complete response (11.1%), 3 partial responses (33.3%), 2 unchanged lesions (22.2%) and 3 progressions (33.3%). Patients with local recurrence had a better response. Median remission duration was 7.5 months in CR + PR patients. Median overall survival was 8+ months; 14+ months for responders and 4 months for nonresponders. The major toxic effects were nausea/vomiting and alopecia; myelosuppression was less frequent and usually not severe.     

Combination Cisplatin and Carboplatin in Advanced Squamous Cell Carcinoma of the Head and Neck

Twenty-three patients with advanced squamous cell carcinoma of the head and neck who had received no prior chemotherapy were treated with carboplatin 350 mg/m² followed by cisplatin 50 mg/m² every 28 days. Twenty-one of 23 patients were evaluablefor response and toxicity. Eight patients (38%) achieved complete response (CR) or partial response (PR) with 2 CR and 6 PR. The overall median survival was 8.4 months (range 19 days-56% months). The major toxicity was hematological with grade III/IV granulocytopenia in 32% and grade III/IV thrombocytopenia in 32%. There was very little nonhematological toxicity and no nephrotoxicity. There were no therapy-related deaths. The combination carboplatin/cisplatin is tolerable in patients with squamous cell carcinoma of the head and neck, with objective responses in 38%; however, the response rate was not superior to single-agent carboplatin or cisplatin. Further studies with a higher dose of cisplatin should be considered.     

伊立替康联合顺铂治疗原发灶不明癌的临床观察

目的 评价伊立替康联合顺铂方案一线治疗原发灶不明癌的疗效及预后相关因素。方法 72例患者入组,2例患者未治疗,70例患者采用伊立替康联合顺铂方案,伊立替康180 mg/m2,静脉滴注,d1;顺铂75 mg/m2,静脉滴注d1~3,21天为一周期。结果 66例可评价疗效,其中4例CR,24例PR,16例SD,22例PD,ORR（CR+PR）为42.4%。中位至进展时间4.5月,中位生存期10.3月,1、2年生存率分别为38.9%和8.3%。最常见的不良反应包括中性粒细胞减少、恶心和呕吐。体能状况评分0-1、转移部位的数目＜3、局限于淋巴结的患者有更长的生存期（P＜0.05）。结论 伊立替康联合顺铂治疗原发灶不明癌安全而有效。体能状况、转移部位的数目、是否局限于淋巴结为原发灶不明癌的重要预后因素。     

Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study

OBJECTIVES: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. METHODS: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m(2)/daily for 5 days every 4 weeks. RESULTS: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14-42%) and 8% (CI = 2-27%), respectively, with a median TTP of 11.7 weeks (CI = 9-22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7-31%). CONCLUSION: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.     

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study.     

Phase II trial of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma

BACKGROUND: This study was undertaken to determine whether the use of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin as first-line therapy increases the proportion of major responders and overall survival in patients with unresectable or metastatic transitional cell carcinoma (TCC) of the urothelial tract. METHODS: Twenty-nine patients with histologically confirmed TCC received methotrexate at a dose of 1000 mg/m2 on Day 1 followed by leucovorin calcium rescue on Day 2 and vinblastine (3 mg/m2), doxorubicin (30 mg/m2), and cisplatin (70 mg/m2) (VAC) on Day 2. Therapy was recycled at 28-day intervals. RESULTS: Fourteen of 28 patients (50%; 95% confidence interval [CI], 31-69%) achieved a major response, including 6 pathologic or clinical complete responses (CR) and 8 partial responses (PR). Nine patients were rendered disease free after postchemotherapy surgical resection of residual disease (surgical CR), including five patients who had PR and four nonresponders to chemotherapy alone. Five of 18 patients with disease limited to lymph nodes attained CR, in contrast to only 1 of 10 patients with visceral metastatic disease. The median survival for the entire population was 13.6 months. CONCLUSIONS: The escalation of methotrexate to 1000 mg/m2 in combination with vinblastine, doxorubicin, and cisplatin did not result in a response proportion or median survival superior to that observed with standard dose M-VAC. As previously observed in a Phase II trial of M-VAC, only the attainment of CR was associated with prolongation of survival.     

放射治疗同时化疗Ⅲ期非小细胞肺癌

目的 评价放射治疗结合不同化疗方案治疗不能手术的Ⅲ期非小细胞肺癌（NSCLC）疗效。方法 62例不能手术的Ⅲ期NSCLC患者随机分为2个组：29例每周接受1次紫杉醇30mg、顺铂30mg化疗（紫杉醇组）,33例每周接受1次依托泊甙（VP-16）100mg、顺铂30mg化疗（VP-16组）。连续5～6周,均同时配合常规分割放射治疗（2Gy/次,5次/周）,照射野包括肺部原发灶和纵隔淋巴引流区,总剂量为60～70Gy。结果 紫杉醇组总有效（CR PR）为82.8%,完全缓解（CR）率为10.3%,VP-16组总有效率为54.6%,CR率为18.0%。2个组总有效率差异有显著性意义(X^2=4.41,P=0.038）。中位生存期、1、2年生存率紫杉醇组分别为12.8个月、52.2%、27.3%,VP-16组分别为9.8月、42.8%、18.4%,2个组差异无显著性意义。化疗的毒副作用主要是骨髓抑制和消化道反应,但均可耐受。结论 紫杉醇组治疗不能手术的Ⅲ期NSCLC近期有效率明显优于VP-16组,但不提高生存率。     

Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non-small cell lung cancer

The purpose of the study was to evaluate the effectiveness in terms of response rates, toxicity and survival of the combination chemotherapy regimen cisplatin and epidoxorubicin (epirubicin) including medroxyprogesterone acetate (MPA), recombinant IL-2 (rIL-2) and antioxidants in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC). Thirty-three chemotherapy-naive patients with NSCLC were enrolled in the study and 30 of them were evaluable. The mean age of the patients was 61 years. Twenty (66.7%) out of 30 patients were >or=60 years, and 5 (16.7%) patients were >or=70 years. The ECOG performance status was 0 to 1 in 30 patients and 2 in 3 patients. Twenty-six patients (78.8%) had stage IIIB disease and 7 (21.2%) had stage IV; histology was mainly squamous cell carcinoma (72.7%). The treatment consisted of cisplatin 40 mg/m2/week and epirubicin 40 mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally and N-acetyl cysteine 1.8 g/day orally. The treatment was administered for 6 weeks. Patients with a complete response (CR), partial response (PR) or stable disease (SD) continued the treatment, according to response re-evaluation, until 15 weeks. The present study reports the results of 6, 9, 12 and 15-week treatment. After 6 weeks, 30 patients were assessable for response: no CR was observed, a PR was achieved in 15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were observed (ORR 30.0%). The median follow-up period was 13 months. The median duration of response was 9 months. The median overall survival (OS) was 15 months. The one-year survival rate was 55.8%. The median progression-free survival (PFS) was 10 months. The toxicity was, as expected, mainly hematologic: neutropenia was the most significant symptom. The non-hematologic toxicity was quite low. Therefore, the treatment's toxicity was quite acceptable. There was no toxic death. The 30.0% ORR, the 15 month OS and the 10 month PFS obtained in this study are comparable with those observed with cisplatin plus epirubicin (ORR 39-54%) in phase II studies and in a previous phase III study (ORR 33%, OS 10.5 months). Moreover, the toxicity was acceptable and it was mainly hematologic. Serum levels of proinflammatory cytokines significantly decreased after treatment.