Biweekly administration of docetaxel and vinorelbine as second-line chemotherapy for patients with stage IIIB and IV non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 013-02)

The current report aims to evaluate the efficacy and safety profile of a biweekly administration of docetaxel and vinorelbine to patients with advanced non-small cell lung cancer, who had previously been treated for this disease. In a prospective, multicenter, open-label, phase II trial, patients received 40 mg/m of docetaxel and 20 mg/m of vinorelbine on days 1 and 15, every 28 days. Treatment continued for up to a maximum of six cycles, unless disease progression or unacceptable toxicity occurred, or consent was withdrawn. Fifty patients were enrolled in the study and they received 174 cycles of chemotherapy, with a median of three cycles per patient. All patients were evaluated for efficacy and toxicity in an intention-to-treat analysis. The overall response rate was 10% [95% confidence interval (CI): 1-19], including one complete response (2%) and four partial responses (8%). Previous chemotherapy of 80% of the responders included paclitaxel. Median time to disease progression was 2.7 months (95% CI: 2.2-4.3) and median overall survival was 6.5 months (95% CI: 2.5-9.2). The survival rates at 1 and 2 years were 18% (95% CI: 7-29) and 4% (95% CI: 0-10), respectively. The most frequent severe toxicities were neutropenia (20% of patients) and leukopenia (8% of patients). Other toxicities appeared in 4% or fewer of the patients. Biweekly administration of docetaxel and vinorelbine is feasible as a second-line treatment for non-small cell lung cancer patients, but its level of activity and toxicity does not suggest any advantage compared with the results obtained with single-agent docetaxel in the same setting.     

Phase II study of S-1 monotherapy as a first-line treatment for elderly patients with advanced nonsmall-cell lung cancer: the Central Japan Lung Study Group trial 0404

Although S-1 has been shown to have activity against advanced nonsmall-cell lung cancer (NSCLC), its efficacy for elderly patients remains unclear. This phase II study evaluated the efficacy and safety of S-1 as a first-line treatment for elderly patients. Chemotherapy-na?ve patients aged 70 years or older with stages IIIB to IV or postoperative NSCLC and performance status 1 or lower were eligible. Patients received S-1 approximately equivalent to 80 mg/m/day for 2 weeks followed by a 1-week rest period every 3 weeks. The primary end point was the response rate. Secondary end points were toxicity, disease control rate, progression-free survival, and overall survival. Twenty-nine patients were eligible. The median age was 78 years (range, 70-85 years). The overall response rate and the disease control rate were 27.6 [95% confidence interval (CI), 11.3-43.9%] and 65.5% (95% CI: 48.2-82.8%), respectively. The median progression-free survival time was 4.0 months (95% CI: 4.0-9.8 months). The median overall survival was 12.1 months (95% CI: 13.8-25.5 months) and the 1-year survival rate was 53.6%. No grade 4 toxicities were observed. The only hematological toxicity of grade 3 was anemia in 6.9% of patients. The grade 3 nonhematological toxicities included hyponatremia, anorexia, nausea, oral mucositis, and diarrhea in 3.4% of patients and infection in 6.9% of patients. S-1 monotherapy was effective and well tolerated as a first-line treatment for elderly patients with advanced NSCLC. The results of this study warrant further investigations of this regimen, including a randomized controlled trial.     

Phase II study of gemcitabine as first-line chemotherapy in patients with advanced or metastatic breast cancer

In this phase II study, the efficacy and tolerability of gemcitabine were studied in 42 patients with locally advanced or metastatic breast cancer who had received up to one prior chemotherapy regimen in an adjuvant setting. Ten patients had received adjuvant chemotherapy. Twenty-eight patients (67%) had visceral disease spread at entry. Gemcitabine (1000 mg/m2) was administered weekly on days 1, 8 and 15 of a 28-day cycle. The mean number of completed cycles was 3.9 and the mean dose delivered was 942.2 mg/m2. Ninety-seven percent of injections were administered as assigned. No complete responses were observed, but there were six partial responses and 24 patients with stable disease lasting 2-9 months. The overall response rate was 14.3% (95% CI 5.4-28.5%). The median survival for all patients was 15.2 months. Maximum WHO grade 3 and 4 toxicities were observed in five patients for nausea and vomiting, one patient for diarrhea, one patient for pain, seven patients for alanine transaminase, and eight patients for segmented neutrophils. There were no grade 3 and 4 toxicities for alopecia. These data confirm modest single-agent gemcitabine activity in advanced or metastatic breast cancer. Gemcitabine's favorable toxicity profile makes it an ideal candidate for combination chemotherapy.     

紫杉醇联合顺铂治疗晚期食管鳞癌临床观察

目的 观察紫杉醇联合顺铂治疗晚期食管鳞癌的疗效及不良反应.方法 用紫杉醇注射液175mg/m2静脉滴注3h,第1天;顺铂25mg/m2,静脉滴注,第1-3天.该方案治疗25例晚期食管鳞癌,3周为1个周期.结果 25例患者共完成化疗周期数为104个,其中完全缓解1例(4.1％),部分缓解10例(41.7％),稳定9例(37.5％),进展4例(16.7％),总有效率为45.8％(11/24).至末次随访,死亡20例,全组中位生存期11.0个月(95％CI:8.35～13.65个月),1年生存率37.3％.12例治疗有效病例的中位生存期为12.5个月(95％CI:9.11～ 15.90个月),治疗无效病例的中位生存期为8.0个月(95％CI:5.50～9.50个月),获治疗有效病例的中位生存期显著好于无效病例(P =0.022).主要毒副反应有:白细胞减少(Ⅲ度7例,Ⅳ度1例)、中性粒细胞减少(Ⅲ度5例,Ⅳ度1例)、血小板下降(Ⅲ度1例)和脱发(Ⅱ度19例).结论 紫杉醇联合顺铂方案治疗晚期食管癌有效安全,可作为晚期食管鳞癌首选化疗方案.     

Treosulfan and gemcitabine in metastatic uveal melanoma patients: results of a multicenter feasibility study

No effective treatment currently exists for metastatic uveal melanoma. However, recent results obtained by an ATP-based tumor chemosensitivity assay have shown consistent activity of treosulfan+gemcitabine in up to 80% of tumor specimens tested. In this study we describe the first clinical results observed with this drug combination at different European centers in patients with metastatic uveal melanoma. Clinical case series of patients with metastatic uveal melanoma were treated with treosulfan+gemcitabine at seven different centers. Fourteen patients, 13 previously untreated and one pretreated with chemoimmunotherapy, were included in the study. Patients received treosulfan+gemcitabine in four different dose regimens. The response rates, progression-free and overall survival, and toxicity were evaluated. The analysis of 14 patients revealed one complete response, three partial responses and a stable disease in eight cases. The objective response rate was 28.6%, the median overall survival was 61 weeks [95% confidence interval (CI) 54-133 weeks], the progression-free survival was 28.5 weeks (95% CI 13-62 weeks) and the 1-year survival rate was 80%. The drugs were well tolerated. The most common side-effects were leuko- and thrombocytopenia. These preliminary results suggest potential therapeutic benefit of treosulfan+gemcitabine treatment in metastatic uveal melanoma and warrant further controlled studies.     

长春瑞滨联合卡培他滨治疗蒽环类及紫杉类耐药的转移性三阴乳腺癌的临床观察

目的观察长春瑞滨联合卡培他滨治疗蒽环类及紫杉类耐药的转移性三阴性乳腺癌患者的疗效和不良反应。方法 32例蒽环类及紫杉类耐药的复发转移性三阴性乳腺癌患者接受长春瑞滨联合卡培他滨化疗,长春瑞滨25mg/m2,静脉滴注,第1天和第8天,采用深静脉穿刺置管技术静脉滴注;卡培他滨825～1000mg/m2,口服,每天2次,第1～14天;21d重复。统计分析其疗效与不良反应。结果 32例患者共接受152个周期治疗,中位治疗周期数为4个周期(2～6个周期);11例患者获得部分缓解(PR,占34.4%),9例患者获得稳定(SD,占28.1%),其中5例患者稳定维持6个月以上;12例患者获进展(PD,占37.5%)。总有效率(CR+PR)34.4%(11/32),疾病控制率(PR+SD)62.5%(20/32),中位疾病进展时间(TTP)为5.4个月。常见不良反应为骨髓抑制,恶心、呕吐和手足综合征等。结论长春瑞滨联合卡培他滨方案近期疗效好,毒性可以耐受,可作为蒽环类及紫杉类耐药的转移性三阴性乳腺癌患者治疗的选择。     

Evaluation of Tomudex in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group study

A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1-19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population.     

Phase II study of gemcitabine plus cisplatin in metastatic breast cancer

Our objectives were to assess the efficacy and toxicity of gemcitabine plus cisplatin as first-line therapy in metastatic breast cancer (MBC). Patients with stage IV MBC and no prior chemotherapy for metastatic disease were treated with gemcitabine 1200 mg/m on days 1 and 8, and cisplatin 75 mg/m on day 1 every 21 days. Up to 6 cycles were given. A total of 46 patients with a median age of 49 years (range 24-77) and Karnofsky performance status of 80 or above were enrolled. In total, 238 cycles were administered. Of the 42 patients evaluable for response, seven (17%) achieved a complete response and 27 (64%) a partial response, for an overall response rate of 81% [95% confidence interval (CI) 69-93%]. Median time to progression was 14.9 months (95% CI 0-30.2 months). Median duration of response was 24.2 months (95% CI 11.2-37.3 months). The median survival was 27.9 months (95% CI 23.1-32.7 months), and the 1- and 2-year survival probabilities were 71.4 and 61.4%, respectively. All patients were evaluable for toxicity, and grade 3/4 WHO toxicities included neutropenia (41.3%), anemia (8.7%), thrombocytopenia (8.7%), alopecia (26.1%) and nausea/vomiting (32.6%). We conclude that gemcitabine plus cisplatin is a highly effective and safe first-line treatment for patients with MBC. The time to progression of 14.9 months compares favorably with other standard treatments (anthracyclines, taxanes). A randomized study is required to further investigate the role of this combination as first-line treatment for MBC.     

Biweekly docetaxel and vinorelbine with granulocyte colony-stimulating factor support for patients with anthracycline-resistant metastatic breast cancer

This phase II trial evaluated the efficacy and toxicity of vinorelbine 25 mg/m2 plus docetaxel 60 mg2/m administered on day 1, every 2 weeks with granulocyte colony-stimulating factor support (G-CSF, 5 microg/kg/day, days 3-7) as primary prophylaxis in patients with histologically confirmed metastatic breast cancer (MBC) and previously treated with anthracyclines in the adjuvant or in the first-line setting. A total of 48 patients received 352 cycles (median 8, range 2-10). All patients were included in the efficacy and safety evaluation on an intent-to-treat analysis. Eight patients (17%) showed a complete response and 14 patients (29%) showed a partial response. Overall response rate was 46% [95% confidence interval (CI) 33-60]. The median duration of response was 10.0 months. With a median follow-up of 18.0 months, the median time to progression was 11.9 months and the median overall survival was 27.1 months. The most frequently reported grade 3/4 hematological toxicity was neutropenia (19% of patients, 4% of cycles). Febrile neutropenia was reported in six patients (13%) and 7 cycles (2%), but no toxic deaths were reported. The most common grade 3/4 non-hematological toxicity was asthenia (17% of patients, 6% of cycles) and nail toxicity (15% of patients, 3% of cycles). In conclusion, biweekly docetaxel plus vinorelbine with G-CSF support is active and well tolerated as chemotherapy for patients with MBC resistant to anthracyclines. G-CSF support is recommended for lowering the incidence and severity of neutropenia and febrile neutropenia.     

A phase II open-label trial of apomine (SR-45023A) in patients with refractory melanoma

Summary Metastatic melanoma continues to be a very difficult disease to treat. Options are limited and often have very little impact on the course of the disease. The objective of the current study was to evaluate the efficacy and safety of continuously administered Apomine (SR-45023A), a novel bisphosphonate, in patients with previously treated metastatic malignant melanoma. Adult patients with previously treated metastatic melanoma received Apomine 100 mg orally, twice daily (total dose 200 mg per day) continuously for 28 days (defined as a cycle). Treatment was continued until disease progression or unacceptable toxicity. A total of 42 patients received at least one dose of Apomine. Stable disease was achieved in 2 patients (5%). No complete or partial responses were observed. Progression free survival of at least 16 weeks was observed in 6 patients (14%). The median overall survival was 6.1 months (95% CI, 4.9–9.4 months). Time to treatment failure was 1.7 months (95% CI, 1.6–1.8 months) with Apomine therapy. By cycle 2, Apomine concentrations reached steady-state. Apomine was well tolerated with only 37% of patients experiencing any drug-related event. Abdominal pain was the most frequent adverse event occurring in 26% of patients. In conclusion, Apomine, at the current dose studied, failed to produce a 30% progression free survival rate at 16 weeks considered to be a meaningful benefit for further development.     

Single-agent capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer

We performed an analysis of the efficacy of capecitabine monotherapy as maintenance treatment for metastatic breast cancer (MBC) after response to capecitabine-based chemotherapy [capecitabine plus docetaxel (XT) or vinorelbine (XN)] as a first-line or a second-line treatment. Sixty-four Chinese patients with histologically confirmed MBC received capecitabine maintenance therapy after disease stabilization or maximal response to capecitabine-based combination chemotherapy. Single-agent capecitabine was administered at a dose of 1000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, every 3 weeks. The median time to progression, the primary endpoint of the study, was 4.4 months (95% confidence interval, 3.4-5.4 months). Fifty-nine patients were evaluable for response. Capecitabine maintenance therapy produced an objective response rate of 5.1% (95% confidence interval, 3.9-6.3%). The incidence of grade 3/4 leukopenia (3.1%) and neutropenia (4.7%) was significantly lower (P<0.001) with capecitabine monotherapy than with combination chemotherapy (46.9 and 54.7%, respectively). Conversely, the incidence of grade 3 hand-foot syndrome was higher with capecitabine maintenance therapy than with combination therapy (14.1 vs. 0%, respectively; P=0.003). Capecitabine monotherapy is an effective maintenance treatment after response to capecitabine-based combination chemotherapy in MBC with a favorable safety profile.     

Phase I/II study of biweekly vinorelbine and oxaliplatin as first-line treatment in patients with metastatic breast cancer

The objective of this phase I/II study was to establish the recommended dose of biweekly vinorelbine and oxaliplatin in patients with metastatic breast cancer and to evaluate the efficacy and safety profile of this schedule as first-line treatment. Four different dose levels of vinorelbine and oxaliplatin were selected for the phase I study: (i) 25 and 80 mg/m2; (ii) 25 and 90 mg/m2; (iii) 25 and 100 mg/m2; and (iv) 30 and 90 mg/m2; respectively. At least three patients were treated at each dose level. Overall, 12 patients were included in the phase I trial. No dose-limiting toxicities occurred at any dose level. Therefore, the fourth dose level (30 mg/m2 of vinorelbine and 90 mg/m2 of oxaliplatin) every 2 weeks was selected for the phase II trial. In this part, 44 patients were included and 61% completed the eight 2-week cycles of study treatment. On an intention-to-treat basis, overall response rate was 59%, and median progression-free survival and overall survival were 9.2 months (95% confidence interval: 7.6-10.9) and 18.6 months (95% confidence interval: 14.4-22.9), respectively. The main severe toxicities were neutropenia (46%) and fatigue (14%). We conclude that the biweekly combination of vinorelbine and oxaliplatin at doses of 30 mg/m2 and 90 mg/m2, respectively, is highly active and well tolerated as first-line treatment for patients with metastatic breast cancer.     

A phase II study of an oxaliplatin/vinorelbine/5-fluorouracil combination in patients with anthracycline-pretreated and taxane-pretreated metastatic breast cancer

The aim of this phase II study was to evaluate safety and efficacy of an oxaliplatin/vinorelbine/5-fluorouracil (FON) combination in anthracycline and taxane-pretreated metastatic breast cancer patients. The following treatment was given: on day 1 of a 21-day cycle, oxaliplatin 130 mg/m (2-h intravenous infusion); on days 1 and 5, vinorelbine [dose level (DL) 1: 17.5 mg/m; DL2: 22 mg/m]; on days 1-5, continuous infusion 5-fluorouracil (DL1: 600 mg/m/day; DL2: 750 mg/m/day). Forty-seven patients were treated (DL1: 43; DL2: 4). Median age was 54 years; 68% had liver metastases, 53% were taxane refractory/resistant and 38% were anthracycline refractory/resistant. Patients received a median of six treatment cycles. Of 46 eligible patients, 16 had partial response; the overall response rate was 34.8% (95% confidence interval 21.3-50.3%), 11 had stable disease lasting more than 4 months. Median follow-up was 13.0 months, median time to progression 5.7 months and estimated overall survival 18.8 months. DL2 was too toxic with three patients having grade 3-4 toxicity, including one death. At DL1, 26 patients (60%) experienced grade 3-4 neutropenia (six febrile neutropenia) and eight had grade 3 oxaliplatin-specific peripheral neuropathy after a median of 646.4 mg/m oxaliplatin (range 124-1619 mg/m). Oxaliplatin (130 mg/m, day 1)/vinorelbine (17.5 mg/m, days 1,5)/5-fluorouracil (600 mg/m/day, days 1-5) demonstrate encouraging activity and a manageable safety profile in anthracycline- and taxane-pretreated metastatic breast cancer patients.     

培美曲塞治疗晚期复发非小细胞肺癌临床观察

目的评价培美曲塞治疗晚期化疗后进展的非小细胞肺癌的疗效和毒副反应。方法46例经病理确诊既往化疗失败的晚期非小细胞肺癌患者,培美曲塞500mg／m^2静脉滴注,第1天,每21d为1个周期,并口服地塞米松、叶酸和肌内注射维生素B12以减轻毒副反应。根据RECIST标准对客观缓解率进行评价,毒副反应评价按美国NCI制定的毒性评价标准。结果46例可评价,总RR为10．6％。疾病控制率为45．7％,中位无进展生存期为3个月,中位生存期为7个月。毒副反应主要是中性粒细胞下降。结论培美曲塞治疗既往化疗失败的晚期非小细胞肺癌,具有较好的疗效和安全性。     

Evaluation of Tomudex in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group study

A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1–19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population.     

Phase II Studies

Summary Eighteen women with metastatic breast cancer previously untreated with chemotherapy were entered on a phase II trial of intravenous menogaril, a new anthracycline derivative. Treatment was given at 140 mg/m² on days 1 and 8 of each 28 day cycle. The most common toxicities were leukopenia in all patients and burning and phlebitis at infusion sites in 72%. Serial assessment of cardiac function by resting and stress gated blood pool scans showed temporary decrements in ejection fraction in only 2 patients (11%). The response rate to the therapy was 19% [95% CI 0–38%] including 1 complete and 2 partial responses. The median time to relapse among responders was 6.5 months. Mean survival in all patients entered was 15.8 months from date of entry. Menogaril at this dose and schedule has modest activity as first line therapy for metastatic breast cancer but also has significant marrow and local toxicity.     

Phase II study of gemcitabine and cisplatin in chemonaive patients with advanced epithelial ovarian cancer

This phase II study evaluated the activity of gemcitabine (Gemzar) plus cisplatin (Platinol) as first-line treatment of advanced epithelial ovarian cancer. Forty-two chemonaive patients with advanced (stage III and IV) epithelial ovarian cancer received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, up to eight cycles. The median number of cycles completed was 5 (range 2-8). Of the 41 patients evaluable for tumor response, 20 had a partial response and nine had a complete response, for an overall clinical and pathologic response rate of 70.7% (95% CI 56.8-84.6%). Median overall survival for all 42 patients was 23.4 months (95% CI 15.9-29.9 months) and the median progression-free survival time was 10.4 months (95% CI 9.4-13.5 months). The combination was generally manageable. Hematologic toxicity (grade 3/4 neutropenia: 31.0/21.4%; grade 3/4 thrombocytopenia: 9.5/4.8%; grade 3/4 anemia: 11.9/0%) and nausea and vomiting (grade 3/4: 35.7/31.0%) were the most common toxicities. There was one toxic death (septic shock due to hematologic toxicity-induced infection). We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer. Further clinical trials with the addition of gemcitabine to first-line treatment appear warranted.     

ET-743: the US experience in sarcomas of soft tissues

Ecteinascidin-743 (ET-743) has shown promise as a new and effective treatment for soft-tissue sarcomas. Two independent, multicenter, Phase II studies have been performed in the USA for patients with unresectable soft-tissue sarcomas (either chemotherapy-na?ve or pretreated patients). The patients received ET-743 at a dose of 1500 micrograms/m2 as a 24 h continuous intravenous infusion every 3 weeks on an outpatient basis. Assessments were conducted every 6 weeks until documented progressive disease, unacceptable toxicity, or withdrawal. Responses were assessed in accordance with conventional oncological criteria and toxicities were graded using the National Cancer Institute common toxicity criteria. A total of 72 patients were enrolled: 36 patients to each study. Confirmed objective response rates were 14% (95% confidence interval (CI) 5 to 30%) and 8% (95% CI 2 to 23%) in chemotherapy-na?ve and pretreated patients, respectively. In chemotherapy-na?ve patients, 12-month progression-free and overall survival rates were 18% (95% CI 4 to 32%) and 49% (95% CI 20 to 78%), respectively. For patients with progressive disease despite prior conventional chemotherapy, 12-month progression-free and overall survival rates were 11% (95% CI 2 to 24%) and 55% (95% CI 35 to 75%), respectively. The median duration of response was 11 months. The durability of major responses in a subset of patients was impressive, as was the number of patients who achieved disease stabilization without showing objective response. Overall, ET-743 had a favorable safety profile. The most common grade 3-4 toxicities included neutropenia and transiently increased transaminase concentrations. ET-743 did not cause alopecia, mucositis, cardiotoxicity or neurotoxicity. The side effects were reversible, non-cumulative and manageable. There were no treatment-associated deaths. In conclusion, ET-743 is an active chemotherapeutic agent that can induce objective responses and clinical benefit in a subset of patients with metastatic or advanced soft-tissue sarcoma.     

A phase II trial of pyrazine diazohydroxide in patients with disseminated malignant melanoma and no prior chemotherapy--Southwest Oncology Group study

Malignant melanoma is rapidly increasing inthe United States. Metastatic diseaseresponds poorly to currently availablechemotherapy. Pyrazine diazohydroxide(PZDH) is a new agent inhibiting DNAsynthesis that is active in mouse tumormodels and human xenografts and lackscross resistance withmultiple standard agents. In this phase IItrial, patients with no prior chemotherapyor immunotherapyfor metastatic disease and performancestatus (SWOG) of 0–1, were treated withpyrazine diazohydroxide at a dose of 100 mg/m²/day by IV bolus injectionover 5–15 minutes for 5 consecutive daysevery 6 weeks. There were 23 eligiblepatients entered on this trial with 74%having PS of 0 and 91% having visceralmetastases. There were no confirmed anti-tumor responses. Theoverall response rate is 0% (95% CI 0%–15%). Median overall survival is sixmonths (95% CI 5-8months). The most common toxicities were hematologic and consisted of lymphopenia,thrombocytopenia, anemia, and leukopenia. Fatigue, and nausea and vomiting were thenext mostcommon toxicities. Pyrazine diazohydroxideby this dose and schedule has insufficientactivity in thetreatment of disseminated malignantmelanoma to warrant further investigation.     

Paclitaxel and cetuximab combination efficiency after the failure of a platinum-based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma

The addition of cetuximab (CTX) to the combination of cisplatin and 5-fluorouracil increases the overall survival (OS) in recurrent/metastatic head and neck squamous cell carcinoma. Only a few patients are eligible for this treatment because of its toxicity. The combination of CTX and paclitaxel (TXL) could be included in sequential treatment strategies. Patients were treated with CTX (400/250 mg/m) and TXL (60-80 mg/m) weekly until disease progression or unacceptable toxicity. Efficacy and safety outcomes were determined retrospectively. A total of 42 patients were included in this analysis. The overall response rate was 38% [95% confidence interval (CI); 23-53%]. The disease control rate with TXL and CTX combination was 74%. Seven (17%) patients progressed before the first evaluation. The median progression-free survival was 3.9 months [95% CI; 3.1-4.7 months] and the median OS was 7.6 months [95% CI; 5.3-9.9 months]. Neurotoxicity and skin rash were the most frequent grade≥2 toxicities, reported in 17 and 12% of patients, respectively. Previous chemotherapy seems to be associated with a lower response rate and progression-free survival but not with the OS. The combination of CTX and TXL was an active and well-tolerated treatment in this series of patients with a poor prognosis and who were mostly symptomatic.