国产培美曲塞联合卡铂治疗蒽环类及紫杉类治疗失败的晚期转移性乳腺癌的临床观察

目的 观察国产培美曲塞联合卡铂治疗蒽环类及紫杉类治疗失败的晚期转移性乳腺癌的疗效及不良反应。方法 2010年3月至2012年1月收治31例蒽环类及紫杉类治疗失败的晚期转移性乳腺癌患者,给予培美曲塞联合卡铂治疗,具体为：培美曲塞500mg／m²静滴,d₁;卡铂AUC=5静滴,d₂,21天为1周期。全组接受至少2个周期化疗,评价疗效与不良反应。结果31例患者均可评价疗效,获PR 12例,SD 10例,PD 9例;RR为38.7％（12／31）,DCR为71.0％（22／31）。KPS评分改善率为67.7％（21／31）。中位肿瘤进展时间为6.0个月（3～14个月）,中位生存期为8.3个月（4～18个月）。主要不良反应为骨髓抑制、消化道反应、疲乏和皮疹,以1～2级为主。结论 培美曲塞联合卡铂治疗蒽环类及紫杉类治疗失败的晚期转移性乳腺癌的疗效较好,不良反应可以耐受,值得临床进一步研究。     

A phase II study of weekly docetaxel in patients with anthracycline pretreated metastatic breast cancer

Background: Docetaxel has significant activity in metastatic breast cancer and weekly schedules are associated with less myelosuppression than 3-weekly schedules. We evaluated the toxicity and the activity of weekly docetaxel in anthracycline-pretreated patients. Patients and methods: A total of 42 patients were studied. Treatment consisted of docetaxel 35 mg/m² weekly as a 30-min infusion for 6 weeks followed by a 2-week rest, with dexamethasone 8 mg i.v. pre-medication and 4 mg orally 12-hourly for 48 h following treatment. Results: The median age of the patients was 53 years (range 34–74). Twenty-six (62%) patients had received prior chemotherapy for advanced disease. Patients received a median 10 weeks of treatment (range 1–24). 11 had a partial response (ORR 26%; 95% CI 13–39%), five of whom had relapsed <12 months since the end of previous anthracycline-based chemotherapy. In addition six patients (14%) had stable disease for >16 weeks. Myelosuppression was rare with only 2 patients (5%) experiencing grade 3 neutropenia (no grade 4 neutropenia). Non-haematological grade III toxicities were as follows: fatigue 17%, neuropathy 0%, hyperlacrimation 5%, stomatitis 7%, diarrhoea 14%, and cutaneous toxicity 19%. Skin toxicity consisted of limb/palmar–plantar erythematous reactions, or fixed-plaque erythrodysaesthesia. Conclusions: Weekly docetaxel has moderate activity in women with anthracycline pre-treated breast cancer. Although the level of myelosuppression is lower than 3-weekly regimens, this weekly regimen cannot be recommended due to the significant non-haematological toxicities associated with the treatment.     

Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer

Purpose To evaluate the efficacy and safety of erlotinib in advanced breast cancer. Experimental design Multicenter, phase II study of erlotinib (150 mg orally daily). Cohort 1: progression after anthracyclines, taxanes, and capecitabine (n = 47). Cohort 2: progression after >1 chemotherapy for advanced-stage disease (n = 22). Primary endpoint was response rate (World Health Organization criteria). Secondary endpoints were safety, time to progression, and survival. Results One patient in each cohort (n = 2, 3.0%) had a partial response. Response duration was 17 weeks for the Cohort 1 patient and 32 weeks for the Cohort 2 patient. Median time to progression was 43 days for Cohort 1 (range 1–204) and 43 days for Cohort 2 (range 25–419). Common adverse events were diarrhea, rash, dry skin, asthenia, nausea, anorexia. Conclusion Erlotinib had minimal activity in unselected previously treated women with advanced breast cancer. Predictive factors are needed to identify breast cancer patients who may derive benefit from erlotinib treatment.     

培美曲塞联合卡铂治疗晚期非鳞型非小细胞肺癌的临床观察

【摘要】目的 探讨培美曲塞联合卡铂治疗晚期非鳞型非小细胞肺癌（NSCLC）的疗效及毒副反应。方法收集55例经病理组织学或细胞学确诊的晚期非鳞型NSCLC患者,接受培美曲塞联合卡铂方案化疗：培美曲塞500mg／m² 静滴,d₁;卡铂AUC=5静滴,d₁或d₂,21天为1周期。每例患者均治疗2个周期以上,观察疗效和毒副反应。结果55例患者均可评价疗效,获CR 4例,PR 14例,SD 20例,PD 17例,有效率为32.7％（18／55）,疾病控制率为69.1％（38／55）;中位无进展生存时间为5.5个月（95％CI：4.4～6.6个月）。亚组分析显示,ECOG评分0～1分者较2分者和初治患者较复治者的近期疗效好（P＜.05）。主要毒副反应包括骨髓抑制、胃肠道反应、乏力和周围神经毒性,以1～2级为主。结论 培美曲塞联合卡铂方案治疗晚期非鳞型NSCLC疗效确切,毒副反应发生率低,耐受较好。     

Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin,pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer

ObjectivesSingle agent maintenance therapy is widely accepted for advanced non-squamous non small cell lung cancer (NSCLC). However, there is no consensus on the initial and maintenance phase regimens, and the clinical benefit of adding bevacizumab to cytotoxic drugs in the maintenance phase remains unclear.MethodsChemotherapy-naïve patients with non-squamous NSCLC were randomly assigned to maintenance therapy with pemetrexed and bevacizumab or pemetrexed alone, after achieving disease control after four cycles of induction therapy with carboplatin (area under the curve = 6), pemetrexed (500 mg/m²), and bevacizumab (15 mg/kg). The primary end-point was 1-year progression-free survival (PFS) rate.ResultsOne hundred ten patients were enrolled in the study, with 55 patients assigned to the two groups. The mean 1-year PFS rate was 43.9% (95% confidence interval [CI]: 29.6–59.2%) in the combination maintenance group and 35.2% (95% CI: 22.1–51.0%) in the pemetrexed maintenance group, and the difference was not significant (p = 0.433). Median PFS measured from enrolment was 11.5 months (95% CI: 7.1–19.0) in the combination maintenance group and 7.3 months (95% CI: 5.7–14.1, hazard ratio: 0.73, 95% CI: 0.44–1.19, log-rank p = 0.198) in the pemetrexed maintenance group. Nasal haemorrhage, hypertension, and proteinuria were significantly more frequent in the combination maintenance group, but they were mild and tolerable.ConclusionBoth maintenance therapy with pemetrexed alone and pemetrexed and bevacizumab in combination were feasible in patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin, pemetrexed, and bevacizumab. According to the selection design, differences in the superiority between these maintenance therapies were not demonstrated.     

A Phase 2 study of perifosine in advanced or metastatic breast cancer

Background First- and second-line chemotherapy with anthracyclines and taxanes in metastatic breast cancer yield a modest improvement in survival with potentially significant toxicity. Subsequent lines of chemotherapy yield response rates of 20–25%, with an unknown impact on survival. Perifosine, an oral alkylphospholipid structurally related to miltefosine, has marked activity against breast cancer cell lines and xenograft models, with broad spectrum cellular effects. Objectives To determine the efficacy and toxicity of perifosine in patients with metastatic breast cancer patients after up to 2 lines of prior chemotherapy for advanced disease. Methods 18 patients were enrolled, and 17 treated, using a loading/maintenance dose schedule, (day 1, 300 mg, maintenance 150 mg days 2–21) every 28 days, until disease progression or unacceptable toxicity. Results Median age of patients was 54 (28–69), 16/17 were female, ECOG performance status was 0/1 in 16 patients. Fifteen received at least 1 prior chemotherapy regimen for metastatic disease (maximum 2). A median of 2 cycles (range 1–13) was administered per patient. Sixteen were evaluable for response: 2 had SD for 4 cycles, 1 SD for 13 cycles, 13 progressed by cycle 2. Grade 3/4 drug-related non-hematologic toxicities include: diarrhea (2), vomiting (2), nausea (2), fatigue (2) and anorexia (1). No grade 3/4 hematologic toxicities were seen. Median time to progression was 8 weeks (7–15 weeks). Conclusion No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months. Supported through NIH/NCI Phase 2 Consortium N01-CM-17107 Grant. N. B. Leighl is the principal investigator. Princess Margaret Hospital Phase 2 Consortium, Ontario, Canada includes Princess Margaret Hospital/University Health Network, Toronto; The Ottawa Hospital Regional Cancer Centre, Ottawa; London Regional Cancer Centre, London; Juravinski Cancer Centre, Hamilton.     

A randomised phase II study of pemetrexed versus pemetrexed + erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer

IntroductionPemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed + erlotinib in patients with advanced non-squamous NSCLC.MethodsNSCLC stage III–IV patients who failed one prior platinum-based chemotherapy regimen, ≥1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status ≤2 were eligible. Patients received pemetrexed 500 mg/m² with vitamin B₁₂ and folic acid q3w alone or combined with erlotinib 150 mg daily. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), time-to-treatment failure (TTTF), response and toxicity.ResultsOf 165 randomised non-squamous patients, 159 were treated (pemetrexed: 83; pemetrexed + erlotinib: 76). The median PFS (months; 95% CI) was 2.89 (1.94, 3.38) for pemetrexed versus 3.19 (2.86, 4.70) for pemetrexed + erlotinib (hazard ratio [HR] 0.63; 95% CI: (0.44, 0.90); P = 0.0047). The median OS (months; 95% CI) was 7.75 (5.29, 10.41) for pemetrexed versus 11.83 (8.18, 16.66) for pemetrexed + erlotinib (HR: 0.68; 95% CI: 0.46, 0.98; P = 0.019). The median TTTF (months: 95% CI) was 2.4 (1.74, 2.99) for pemetrexed versus 3.0 (2.23, 4.07) for pemetrexed + erlotinib (HR 0.64; 95% CI: 0.46, 0.89; P = 0.0034). One patient died in pemetrexed + erlotinib arm due to febrile neutropenia. Grades 3/4 drug-related toxicities (in ≥5% of patients) in pemetrexed/pemetrexed + erlotinib were febrile neutropenia (2.4%/10.5%), diarrhoea (1.2%/5.3%), rash (1.2%/9.2%); anaemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%).ConclusionsPemetrexed + erlotinib treatment significantly improved PFS, OS and TTTF in 2nd line non-squamous NSCLC and was associated with an increase in grade 3/4 toxicities compared with pemetrexed alone.     

A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer

Aim

To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC).

Patients and methods

The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m² (day 1), docetaxel 30 mg/m² (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF).

Results

The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to <50%, with a decrease from baseline >15%. LVEF median values remained stable from baseline to the end of the study (60%).

Conclusions

The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.     

First-line paclitaxel and cisplatin used sequentially or in combination in metastatic breast cancer: A phase II randomized study

Introduction

Breast cancer (BC) is the commonest cancer among females worldwide. Some patients present initially at advanced stages and more than 50% of them will develop metastasis (MBC) at some point. Compared to single agents, combination chemotherapy produces higher response rates (RR), longer progression-free survival (PFS) than single agents. This is associated with remarkably higher toxicities. At the same time, overall survival (OS) is comparable. This study aimed to compare safety and efficacy of combination and sequential chemotherapy.

培美曲塞联合卡铂和吉西他滨联合卡铂一线治疗晚期非鳞非小细胞肺癌的疗效观察

目的探讨培美曲塞联合卡铂治疗晚期非鳞非小细胞肺癌的临床效果和安全性。方法选取晚期非鳞非小细胞肺癌患者90例,随机分为两组,对照组43例,给予吉西他滨联合卡铂治疗;观察组47例,给予培美曲塞联合卡铂治疗。对两组患者治疗效果进行评价,并统计不良反应发生情况。结果观察组与对照组患者全部完成2、4或者6个周期化疗,对照组患者中有2例因消化道不良反应严重而终止治疗。观察组患者临床有效率明显高于对照组,差异有统计学意义(P<0.05),两组患者疾病控制率差异无统计学意义(P>0.05)。观察组患者粒细胞减少和肝功能损害者明显少于对照组,且不良反应发生率明显少于对照组,两组差异有统计学意义(P<0.05)。结论与吉西他滨联合卡铂的治疗方案相比,培美曲塞联合卡铂治疗晚期非鳞非小细胞肺癌的临床疗效更好,安全性也更高。     

Phase II study of gemcitabine plus paclitaxel in metastatic breast cancer patients with prior anthracycline exposure

Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. Patients and Methods: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m² was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m² was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. Results: Objective response rate was 41.7 percent (95 percent CI: 21.9-61.4) with 16.7 percent (95 percent CI: 1.7-31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6-42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3-4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. Conclusion: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.     

A phase II study of capecitabine plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer

PURPOSE: This open-label, multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus gemcitabine combination chemotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: We enrolled 63 patients who received capecitabine 830 mg/m(2) orally twice daily on days 1-21 plus gemcitabine 1000 mg/m(2) as a 30-min infusion on days 1, 8 and 15 every 4 weeks for up to six cycles. RESULTS: A total of 14 patients had partial responses giving an overall response rate of 22% (95% confidence interval [CI] 13-34%) in the intent-to-treat population. The median time to progression and overall survival were 3.9 months (95% CI 3.5-5.7) and 7.5 months (95% CI 5.0-10.0), respectively, and 1-year survival rate was 27.1% in the intent-to-treat population. Capecitabine plus gemcitabine was well tolerated. Grade 3 hematological adverse events were neutropenia (21%) and thrombocytopenia (2%); the only grade 4 hematological events were anemia (2%) and neutropenia (6%). Non-hematological adverse events were mainly gastrointestinal events and hand-foot syndrome, which affected 16% of patients. Grade 3/4 non-hematological events were infrequent. CONCLUSION: The combination of capecitabine plus gemcitabine appears to be active and well tolerated as first-line treatment in patients with advanced/metastatic pancreatic cancer.     

Phase I/II pharmacokinetic study of pemetrexed and epirubicin in patients with locally advanced or metastatic breast cancer

BACKGROUND: Pemetrexed and epirubicin are each active in patients with advanced/metastatic breast cancer (MBC). This phase I/II study evaluated these drugs as a combination regimen. PATIENTS AND METHODS: Women with locally advanced or MBC were enrolled. Pemetrexed 400-600 mg/m2 and epirubicin 60-90 mg/m2 were administered on day 1 every 21 days. The recommended phase II dose was evaluated in a 2-stage design. RESULTS: Phase I enrolled 34 patients and evaluated 5 dose levels. Dose-limiting toxicities were neutropenia and febrile neutropenia. Patients received a median of 7.5 cycles (range, 1-8 cycles), and promising efficacy (partial response [PR], 32%; stable disease [SD], 50%) was observed. Pharmacokinetics of pemetrexed was unchanged when combined with epirubicin. Selected phase II regimen (pemetrexed 600 mg/m2 and epirubicin 75 mg/m2) was administered to 22 patients (median, 4.5 cycles; range 1-13 cycles). Five patients experienced a PR (23%), and 10 experienced SD (46%). This response was below the predefined efficacy requirements for subsequent enrollment, and accrual was stopped. Median time to progression was 5.3 months (95% CI, 3.1-8.9 months), and median time to treatment failure was 3.5 months (95% CI, 2.6-5.9 months). CONCLUSION: The regimen is safe but cannot be recommended as first-line chemotherapy in advanced breast cancer because of the low response rate.     

培美曲塞联合卡铂在鼻咽癌二线治疗中的临床研究

目的观察培美曲塞联合卡铂在鼻咽癌二线治疗中的临床疗效和不良反应。方法培美曲塞500 mg/m2,第1天;卡铂,AUC5,第1天,21 d为1个周期。所有病例均接受至少2个周期的化疗。结果 14例患者入组,均可评价疗效,CR 1例,PR 3例,RR为28.6%(4/14),SD为35.7%(5/14),PD为35.7%(5/14)。中位随访时间6个月,中位TTP 3.5个月,1年生存率为35.7%。主要不良反应为骨髓毒性、疲乏,3例(21.4%,3/14)发生了Ⅲ~Ⅳ度白细胞减少;2例(14.3%,2/14)发生了Ⅲ度血小板减少;2例(14.3%,2/14)发生了Ⅲ度疲乏。结论培美曲塞联合卡铂方案二线治疗复发或转移性鼻咽癌有较好的疗效,患者耐受性好,值得临床进一步研究。     

A phase I study of pemetrexed (ALIMTA) and cyclophosphamide in patients with locally advanced or metastatic breast cancer.

PURPOSE: Determine the maximum tolerated dose (MTD) of pemetrexed and cyclophosphamide combination therapy for patients with locally advanced or metastatic breast cancer. EXPERIMENTAL DESIGN: Patients with locally advanced or metastatic breast cancer and WHO performance status 0 to 2 were eligible. Pemetrexed (range, 400-2,400 mg/m(2)) was administered on day 1 of a 21-day schedule followed by cyclophosphamide (range, 400-800 mg/m(2)). Folic acid and vitamin B(12) supplementation began 1 to 2 weeks before the first pemetrexed dose. RESULTS: Fifty-seven pretreated patients were enrolled and received 342 cycles (median, 4 cycles; range, 1-26) through 14 dose levels. The MTD of pemetrexed was 2,400 mg/m(2) (combined with cyclophosphamide, 600 mg/m(2)) with dose-limiting toxicities of grade 4 neutropenia with grade 4 infection and grade 3 diarrhea. Other grade 3 or 4 toxicities included (febrile) neutropenia, thrombocytopenia, anemia, elevated alanine aminotransferase/aspartate aminotransferase, and diarrhea. Pharmacokinetic analysis indicated that pemetrexed clearance and central volume of distribution were 40% lower than single-agent reference data, yielding a 68% increase in total systemic exposure and a 56% increase in maximal plasma concentration. Among the 50 patients evaluable for efficacy, 13 (26%) patients had a partial response and 17 (34%) patients had stable disease. CONCLUSIONS: Pemetrexed was generally well tolerated. The observed toxicities were consistent with the known toxicity profiles of pemetrexed and cyclophosphamide. Considering the MTD and the toxicity and efficacy results in this and prior studies, a low (600 mg/m(2)) and a high (1,800 mg/m(2)) dose of pemetrexed with cyclophosphamide (600 mg/m(2)) will be evaluated in the consecutive prospective randomized phase II study.     

国产培美曲塞联合卡铂一线治疗老年Ⅳ期肺腺癌的临床研究

目的 探讨老年Ⅳ期肺腺癌患者采用国产培美曲塞联合卡铂一线治疗的疗效及安全性。方法 2009年7月至2011年12月收治49例老年Ⅳ期肺腺癌患者,给予国产培美曲塞联合卡铂一线化疗,具体方案为：培美曲塞500mg／m2 静滴,d1;卡铂 AUC=5 静滴,d1,21天为1个周期。每2个周期评价近期疗效并随访远期疗效,对相关指标的疗效进行分层分析,记录毒副反应。结果 48例患者可评价疗效,获PR 11例,SD 20例,PD 17例,有效率（RR）为22.9％,疾病控制率（DCR）为64.6％;48例可评价疗效的患者均获随访,中位无进展生存时间（PFS）为6.5个月（95％CI：5.7～7.3个月）,中位总生存时间（OS）为11.3个月（95％CI：10.6～11.9个月）;将年龄、性别、ECOG PS评分、吸烟状态、转移器官数目以及有无骨转移、恶性胸腔积液、脑转移共8个指标分层,其中ECOG PS评分、吸烟状态、转移器官数目分层间RR、PFS或OS的差异有统计学意义（P＜0.05）。49例患者的主要毒副反应为1～2级骨髓抑制和胃肠道反应,无1例需降低剂量强度或出现化疗相关性死亡。结论 国产培美曲塞联合卡铂化疗方案的临床获益显著且安全性高,是一线治疗老年Ⅳ期肺腺癌患者的较好选择。     

Phase II study of sunitinib as maintenance therapy in patients with locally advanced or metastatic non-small cell lung cancer

This open-label, phase II study evaluated the antitumor activity and safety of sunitinib monotherapy as maintenance treatment following first-line chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Following treatment with standard doublet chemotherapy (paclitaxel and carboplatin), patients received oral sunitinib (starting dose 50 mg/day) in 6-week cycles (Schedule 4/2: 4 weeks on treatment, 2 weeks off treatment) until disease progression, unacceptable toxicity or withdrawal of consent. The primary endpoint was probability of survival at 1 year ≥55%. Of 84 patients who received first-line chemotherapy, 66 (79%) received sunitinib maintenance therapy (median sunitinib cycles started: 2 [range 1-20]). Probability of survival at 1 year was 40.5% (95% confidence interval [CI]: 29.8, 51.0). Median overall survival was 10.4 months (95% CI: 8.0, 12.2). The objective response rate was 27.4% (95% CI: 18.2, 38.2). The most frequently reported all-causality adverse events of any grade during sunitinib maintenance therapy were fatigue/asthenia (55%), diarrhea (36%), and nausea (32%). These data suggest that maintenance therapy may have value in NSCLC, although the primary endpoint of the study was not met.     

A phase II study of pemetrexed disodium (LY231514) in patients with locally recurrent or metastatic breast cancer

A phase II study was conducted to evaluate the activity of pemetrexed in patients with locally recurrent or metastatic breast cancer. 38 patients, median age 52 years (range 36–71 years), were given pemetrexed 600 mg/m² as a 10-min intravenous (i.v.) infusion every 3 weeks. Median time from diagnosis to study entry was 48 months (range 14.7–310 months). 33 of 38 patients had prior chemotherapy; 16 adjuvant, 12 metastatic and 5 in both settings. Sites of disease included skin and soft tissue (19/38) nodes (18/38), lung (17/38), liver (13/38) and bone (3/38). An overall response rate of 28% (95% confidence interval (CI): 14.2–45.2%) in 10/36 evaluable patients (1 complete response (CR), 9 partial responses (PR)), included reductions in hepatic and pulmonary metastases. 5 of 10 responders had received taxoid or anthracycline therapy for metastatic disease; 3 of these 5 had also received adjuvant chemotherapy. Median duration of response was 8 months (range 1.6–14+ months), and median survival was 13 months (95% CI 9.56–17.38 months). 167 courses were given (median five per patient; range 1–9), with 37 reductions and 33 delays. Reasons for reduction included neutropenia (11%) and mucositis (5%), with delays due to raised LFTs (21%), neutropenia (12%) and other non-treatment related events. The major haematological toxicities (Common Toxicity Criteria) (CTC) were grade 3/4 neutropenia (47%) and thrombocytopenia (15.7%) of patients. There was one report of a grade 3 infection. Non-haematological toxicities (all grades 2/3) included elevated transaminases (92%), vomiting (34%), nausea (34%) and mucositis (32%). One episode of grade 4 diarrhoea was reported. Other toxicities included a skin rash, grade 2 (42%), 3 (5%) and 4 (13%), which was ameliorated by the use of prophylactic dexamethasone. These results suggest that pemetrexed has significant antitumour activity in advanced breast cancer with responses in patients who had previously received anthracyclines and taxoids.