A phase 2 trial of bevacizumab and high-dose interferon alpha 2B in metastatic melanoma

Bevacizumab is a humanized recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, an agent with proangiogenic effects in melanoma. Interferon alpha (IFN-α) has antiangiogenic properties through its ability to downregulate basic-fibroblast growth factor levels. We hypothesized that the coadministration of these agents would lead to tumor regression. Patients with metastatic melanoma received bevacizumab 15 mg/kg intravenously on day 1 of the 2-week cycle. IFN-α was administered thrice weekly at 5 MU/m subcutaneously during cycle 1 and was increased to 10 MU/m during cycle 2. Patients were restaged every 6 cycles. Patients with stable disease or a response continued with therapy. Baseline serum vascular endothelial growth factor and fibroblast growth factor were measured. Twenty-five patients were accrued. Mean age was 58.4 years. Eleven patients required IFN-α dose reductions due to toxicity. Common grade 3 toxicities associated with IFN-α included fatigue and myalgia. Bevacizumab administration was associated with grade 2-3 proteinuria in 6 patients. Grade 4 adverse events were pulmonary embolus (1), myocardial infarction (1), and stroke (1). Six patients had a partial response, and 5 patients exhibited stable disease that lasted more than 24 weeks (range: 30 to 122 wk). Median progression-free survival and overall survival were 4.8 and 17 months, respectively. Significantly lower fibroblast growth factor levels were observed in patients with a partial response compared to those with stable or progressive disease (P=0.040). Administration of bevacizumab with IFN led to a clinical response in 24% of patients with stage IV melanoma and stabilization of disease in another 20% of patients. This regimen has activity in advanced melanoma.     

Maintenance immunotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck

The purpose of this study was to determine the efficacy and safety of a maintenance immunotherapy regimen administered to patients with recurrent/metastatic squamous cell carcinoma of the head and neck (RMHN) who showed clinical benefit from docetaxel, ifosfamide, and cisplatin chemotherapy (DIP). Every 4 weeks, patients with RMHN received 60 mg/m docetaxel on day 1, and 1200 mg/m ifosfamide and 20 mg/m cisplatin on days 1 to 4. Low-dose subcutaneous interleukin-2 and oral 13-cis-retinoic acid were administered as maintenance immunotherapy to patients who showed a clinical benefit (complete or partial response, disease stability). The primary end point was response; secondary end points were progression-free survival, overall survival, toxicity, and evaluations of lymphocytes, natural killer cells, and serum vascular endothelial growth factor (VEGF). After a median follow-up of 22 months, 263 courses of chemotherapy were administered to the 54 patients. The overall response rate was 59%. Forty-two patients (78%) had a clinical benefit and received 185 courses of maintenance immunotherapy. Median progression-free survival and overall survival were 11.1 and 21.8 months, respectively. Statistically significant, progressive increases in lymphocytes and natural killer cells and a decrease in VEGF were observed in patients treated with maintenance immunotherapy. The toxicity was relatively well tolerated and caused no death. Outpatient administration of DIP, followed by low-dose interleukin-2 and 13-cis-retinoic acid, was generally well tolerated and showed promising activity against RMHN. Longitudinal changes in lymphocytes, natural killer cells, and VEGF might be useful biomarkers for response and survival.     

周剂量多西紫杉醇联合顺铂二线治疗进展期胃癌的临床研究

目的 研究多西紫杉醇(TXT)联合顺铂(DDP)方案二线治疗进展期胃癌的疗效和毒副作用.方法 既往应用FOLFOX4或XELOX方案化疗进展的晚期胃癌患者36例,采用多西紫杉醇(艾素)35 mg/m2,第1、8天,静滴;顺铂20 mg/m2,第1～5天,静滴,21 d为1个周期.结果 36例患者中,CR 0例,PR 10例,SD 12例,PD 14例,客观有效率(CR+PR)27.8%,中位生存期6.5个月,中位肿瘤进展时间4.4个月.毒副作用主要为中性粒细胞减少.结论 多西紫杉醇联合顺铂方案二线治疗进展期胃癌有效率较高,有生存优势,毒副作用可耐受.     

周剂量多西紫杉醇联合顺铂二线治疗进展期胃癌的临床研究

目的研究多西紫杉醇（TXT）联合顺铂（DDP）方案二线治疗进展期胃癌的疗效和毒副作用。方法既往应用FOLFOX4或XELOX方案化疗进展的晚期胃癌患者36例,采用多西紫杉醇（艾素）35mg／m2,第1、8天,静滴;顺铂20mg／m2,第1～5天,静滴,21d为1个周期。结果36例患者中,CR0例,PR10例,SD12例,PD14例,客观有效率（CR＋PR）27．8％,中位生存期6．5个月,中位肿瘤进展时间4．4个月。毒副作用主要为中性粒细胞减少。结论多西紫杉醇联合顺铂方案二线治疗进展期胃癌有效率较高,有生存优势,毒副作用可耐受。     

Activity of cladribine combined with etoposide in heavily pretreated patients with indolent lymphoid malignancies

We determined the effectiveness and toxicity of combined chemotherapy consisting of etoposide 100 mg/m(2)/day i.v. and cladribine (2-CdA) 0.12 mg/kg/day i.v. each for 5 days (EC regimen) in the treatment of refractory or relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. The cycles were repeated every 28 days, reaching a maximum of six courses. Twenty patients entered the study. All patients had received three or more cycles of chemotherapy before the EC regimen (median 8, range 3-19). Thirteen patients received 2-CdA before the EC regimen. Seven out of 20 patients (35%) responded, including one complete response. Median overall survival time of responding patients was 22 months (range 3-30). Myelosuppression and infections were the major toxicity of the EC regimen.     

R-CHOP方案治疗17例弥漫大B细胞型淋巴瘤临床观察

目的研究利妥昔单抗联合CHOP方案治疗弥漫大B细胞型淋巴瘤的疗效和不良反应。方法17例弥漫大B细胞型淋巴瘤(DLBCL)共接受6个周期R-CHOP方案的治疗:利妥昔单抗375mg/m2第1天,环磷酰胺750mg/m2第2天,阿霉素50mg/m2第2天,长春新碱1.4mg/m2第2天,泼尼松100mg/d第2～6天。结果总缓解率为82.4%,其中完全缓解9例,完全缓解率为52.9%,5例达到部分缓解,部分缓解率29.4%。17例患者1年和2年无进展生存率分别为82.4%(14/17)和58.8%(10/17),1年和2年的总生存率分别为94.1%(16/17)和76.5%(13/17)。其不良反应主要为骨髓抑制,仅1例出现利妥昔单抗输注相关反应。结论R-CHOP方案治疗弥漫大B细胞型淋巴瘤疗效高而不良反应轻,可作为治疗该病的一线方案。     

A phase II study of docetaxel and infusional cisplatin in advanced non-small-cell lung cancer

BACKGROUND: To evaluate the efficacy and safety of combination chemotherapy of cisplatin (5-day continuous infusion) and docetaxel for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Eligible patients had an ECOG performance status of 0-2 with measurable NSCLC. Patients received continuous infusion cisplatin 20 mg/m2/day on 5 days and bolus docetaxel 60 mg/m2/day (day 1; PiD therapy) at a 4-week interval. RESULTS: Forty-three patients were enrolled. The mean number of cycles administered per patient was 2, and ranged from 1 to 4. The response rate was 49% (95% confidence interval, 33.9-63.8%). The median survival time was 47 weeks and the 1-year survival rate was 47%. The major toxic effects were grade 3 or 4, neutropenia (88%), leukopenia (81%), thrombocytopenia (14%) and anemia (42%). There were no treatment-related deaths. CONCLUSION: PiD therapy was a well-tolerated and active regimen for patients with advanced NSCLC. The major toxicity was neutropenia.     

Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99)

The objectives are to evaluate and compare the response and toxicity of a 3-weekly and a 2-weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second-line treatment in patients with transitional cell carcinoma (TCC). Between June 2000 and July 2001, 30 patients with progressive disease (PD) during first-line chemotherapy (n = 11) or relapse after adjuvant cisplatin-based chemotherapy of a metastatic or locally advanced TCC (n = 18) have been randomised to receive either six cycles (schedule A) of 3-weekly Gem (1000 mg/qm, days 1 and 8) and Pac (175 mg/qm, day 1) or 2-weekly treatment until disease progression (schedule B) with Gem (1250 mg/qm, day 1) and Pac (120 mg/qm, day 2). Restaging was performed after every 6 weeks by clinical imaging. Of 30 patients, one patient in schedule A and two patients in schedule B were not evaluable for response due to serious adverse events (SAEs) during the first cycle. The overall objective response (OR) was 44% (12 of 27) with eight complete remissions (CRs) and four partial remissions. Median time to progression (TTP) was 11 (3-41) months in schedule A and 6 (1-15+) months in schedule B. Median survival was 13 (5-46) months in schedule A and 9 (0-16) months in schedule B. Schedule A showed a significantly higher rate of CRs (7 vs. 1, p < 0.05). With a median number of six (1-6) cycles (A) and nine (1-23) cycles (B), TTP and survival were not significantly different. In schedule B, one patient had WHO grade IV anaemia and leucopenia. WHO grade III toxicities were seen in schedule A/B as follows: anaemia 3 (23%)/2 (16%) patients, leucopenia 5 (38%)/2 (16%), thrombocytopenia 0/2 (16%) and alopecia 10 (76%)/4 (32%). The combination of Gem and Pac is an effective second-line regimen in patients with mainly poor prognosis due to PD after cisplatin-based chemotherapy. Except for three SAEs (uncertainly therapy related), both regimens were tolerated well. The 3-weekly schedule with a nonsplit Pac dose showed a significantly higher complete response rate in our small study population and, thus, might be superior to the 2-weekly schedule.     

A phase II trial of gemcitabine in the treatment of advanced bile duct and periampullary carcinomas

BACKGROUND: Gemcitabine is a novel nucleoside analogue with clinical anticancer activity in several malignancies. From September 1998 to April 2000, we treated patients with advanced bile duct and periampullary carcinomas with gemcitabine alone. METHODS: Gemcitabine 1,000 mg/m(2)/day was administered in 200 ml of normal saline as a 30-min intravenous infusion on day 1 weekly for 3 weeks, followed by a 1-week rest. RESULTS: A total of 24 consecutive patients (15 men, 9 women), with a median age of 59.5 years (range 40-72 years), were enrolled. All patients were evaluable for response: 1 patient achieved complete remission (CR); 2 patients had partial remission (PR); 8 patients remained stable (SD), and 13 patients had progressive disease (PD). The overall response rate (CR + PR) was 12.5% with a 95% confidence interval (CI) of 2.7-32.4%. The median progression-free survival (PFS) was 2.5 months (95% CI 1.6-5.5 months), and the median overall survival (OS) was 7.2 months (95% CI 3.8-8.9 months). Patients with disease control (CR + PR + SD) had better PFS and OS than those with PD. There were no treatment-related deaths. Few patients encountered grade 3/4 toxicity. CONCLUSION: Chemotherapy with gemcitabine demonstrated notable activity and was associated with a well-tolerable toxicity profile in patients with advanced biliary tract malignancies.     

多西紫杉醇联合顺铂治疗晚期非小细胞肺癌

目的：探讨多西紫杉醇联合顺铂治疗晚期非小细胞肺癌（Non-Small Cell Lung Cancer,NSCLC）的临床疗效和不良反应。方法：42例晚期NSCLC患者,采用多西紫杉醇75 mg/m^2加入5%葡萄糖注射液500 mL中静脉滴注1 h,第1天;顺铂25 mg/m^2加入0.9%氯化钠注射液500 mL中静脉滴注,第1-3天。21 d为一个周期,至少二个周期评价疗效。结果：42例患者中,完全缓解（CR）2例,部分缓解（PR）19例,无变化（NC）13例,进展（PD）8例;初治组有效率为54.5%,复治组有效率为45.0%,两组比较,差异无统计学意义（P〉0.05）。中位生存期为10.9个月,中位疾病进展时间为4.8个月,1年生存率为40.5%。Ⅲ-Ⅳ度不良反应：白细胞减少为33.3%,脱发为19.0%,口腔黏膜炎为11.9%。结论：多西紫杉醇联合顺铂治疗晚期非小细胞肺癌有较好的疗效,不良反应轻,耐受性好,值得进一步研究。     

紫杉醇、奥沙利铂联合氟尿嘧啶方案与S1＋奥沙利铂方案在治疗进展期胃癌中的疗效对比研究

目的比较紫杉醇、奥沙利铂联合氟尿嘧啶方案与S1十奥沙利铂方案在治疗晚期胃癌中的临床疗效和安全性。方法选取60例经组织或细胞病理学证实的晚期胃癌患者,随机分为紫杉醇、奥沙利铂联合氟尿嘧啶组（TOF组）和s1十奥沙利铂组（S0x组）,每组30例。TOF组治疗方案为：紫杉醇135mg/m2,第1天,使用前按照说明书要求进行预处理;氟尿嘧啶500rng／m2,化疗泵持续静脉滴注,第1～5天;奥沙利铂100mg／m2,静脉滴注2h,第1天。SOX组治疗方案为：替吉奥胶囊根据体表面积给药,体表面积〈1．25m2,40mg,2次／d;体表面积125～1．50m2,50mg,2次／d;体表面积〉1．50m2,60mg,2次／d,早晚餐后口服,第1～14天;停药7d;奥沙利铂130mg／m2静脉滴注,第1天,21d为一个周期。2个周期后评价疗效并记录毒副作用。结果TOF组客观缓解率为43．3％,疾病控制率为60％,中位无进展生存（PFS）时间为6．5个月;S0x组客观缓解率为36．7％,疾病控制率为56．7％,中位无进展生存（PFS）时间为5．8个月。2组客观缓解率和疾病控制率比较差异无统计学意义。TOF组最常见的不良反应是骨髓抑制、恶心呕吐、口腔黏膜炎,SOX组主要为骨髓抑制。TOF组的不良反应发生率较SOX组更高。结论两种方案治疗进展期胃癌均有成效,紫杉醇、奥沙利铂联合氟尿嘧啶方案不良反应更大,但患者均可耐受。     

FOLFOX6方案治疗晚期食管癌的临床观察

目的 探讨FOLFOX6方案治疗晚期食管癌的疗效.方法 治疗组(n=22)按FOLFOX6方案用药,亚叶酸钙400 mg/m2,第1天;奥沙利铂100 mg /m2,第1天;5-氟脲嘧啶400 mg/m2,第1天;5-氟脲嘧啶2 400～3 000 mg/m2,持 续静脉点滴46 h.同时止吐和对症支持治疗,14 d为...     

Randomized phase 2 study of radiotherapy alone versus radiotherapy with paclitaxel in non-small cell lung cancer

This randomized phase 2 study aimed to assess and compare the toxicity and response rates in patients with unresectable non-small cell lung cancer treated with radiotherapy (1.8-2 Gray [Gy] daily, five fractions a week, total 63 Gy) or radiotherapy + paclitaxel administered weekly (1.8 Gy daily, five fractions a week, total 59.4 Gy). Twelve patients in the latter arm received 30 mg/m2 paclitaxel (median six cycles) over a 3-h infusion once weekly. After assessing toxicity, the remaining nine patients received 60 mg/m2 paclitaxel weekly (median six cycles). Response was evaluated radiologically 1 month after treatment. Grade 3 toxicity was 20% and 38% in the radiotherapy and chemoradiotherapy groups, respectively. Overall survival rates in complete and objective (complete plus partial) responders and progression-free survival rate of the objective responders were significantly better in the chemoradiotherapy arm. We believe that using paclitaxel in concurrent chemoradiotherapy regimens may be effective in patients with unresectable, locoregionally advanced non-small cell lung cancer.     

Comparison of three different regimens in the treatment of acute brucellosis: a multicenter multinational study

The present study was undertaken to evaluate efficacy, safety and patient acceptability of three antibiotic regimens for the treatment of acute brucellosis. Six different centres were involved: three in France, one in Greece and two in Spain. The regimens were: oral rifampicin 900 mg/day plus oral doxycycline 200 mg/day for 45 days (A), oral doxycycline 200 mg/day for 45 days plus im streptomycin 1 g/day for 21 days (regimen B) [corrected] and the WHO regimen (C) combining oral tetracycline 2 g/day for 21 days plus im streptomycin, 1 g/day, for 14 days. Regimens A and B were randomly allocated in all centres, while regimen C was allocated only in two centres. All patients were suffering from acute brucellosis clinically and biologically proven. 143 patients were allocated for treatment and analysed. Their mean age was 41 years (range 13-70), 49 were female and 94 male, and their mean weight was 64 kg (range 35-98). Among these patients, 14% had localized disease (nine orchitis, eight osteo-articular involvement and one pleural effusion), but there was no statistical difference between the three regimens in regard to this localized disease. Forty-five per cent of the patients had positive blood cultures. The cure rate with regimen A was 95%, 96% with regimen B and 59% with regimen C. Thus regimen A presented the same efficacy rate as regimen B, but regimen C cannot be regarded as the treatment of choice for acute brucellosis.     

氟达拉滨和环磷酰胺联合利妥昔单抗治疗慢性淋巴细胞白血病疗效分析

目的 探讨氟达拉滨和环磷酰胺联合利妥昔单抗(FCR方案)治疗慢性淋巴细胞白血病(CLL)的效果.方法 采用FCR方案治疗21例CLL患者,其中10例为初治患者,11例为复治患者.FCR方案为氟达拉滨25 mg/m2,第2～4天,静脉滴注;环磷酰胺250 mg/m2,第2～4天,静脉滴注;利妥昔单抗375 mg/m2,第1天,静脉滴注.每28 d为1个疗程.采用多参数流式细胞术(FCM)检测微量残留病(MRD).同时对治疗前临床特点与完全缓解(CR)率行相关性分析.结果 11例(52.4%)患者获得CR,7例(33.3%)获得部分缓解,总有效率为85.7%;中位随访时间19(7～73)个月,总生存率为86.0%,无进展生存率为72.0%.单变量分析表明治疗前Binet分期为A+B、免疫球蛋白重链可变区基因有突变或ZAP-70阳性细胞率≤20%与高CR率相关;6例患者化疗后MRD低于1%.FCR方案的不良反应主要表现为骨髓抑制和胃肠道反应.结论 FCR方案对CLL的治疗有确切疗效.

Abstract：

Objective To evaluate the efficacy of combination chemoimmunotherapy of fludarabine,cyclophosphamide and rituximab (FCR) in chronic lymphocytic leukemia (CLL). Methods Twenty-one patients with CLL were treated with FCR regimen which consisted of fludarabine (25 mg/m2, days 2 to 4),cyclophosphamide (250 mg/m2, days 2 to 4) and rituximab ( 375 mg/m2, day 1 ) in a course of 28 days.The minimal residual disease (MRD) was determined by multiparameter flow cytometry. The correlation between the pretreatment characteristics and complete remission (CR) rate was analyzed. Results Eleven patients (52.4%) achieved CR, 7 (33.3%) achieved partial remission (PR) with a overall response (OR)rate of 85.7%. With a median follow-up time of 19 (7 -73 ) months, the overall survival (OS) was 86.0%,and the progression-free survival (PFS) was 72.0%. Pretreatment parameters independently associated with higher CR rates were Binet stage A + B, IgVH mutated and ZAP-70 less than 20%. MRD was less than 1% in 6 patients. The most common toxicities were myelosuppression and gastrointestinal reaction. Conclusion FCR is an effective regimen for CLL patients.     

IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.     

DICE方案化疗序贯三维适形放疗治疗鼻腔NK/T细胞淋巴瘤24例的临床观察

目的评价DICE方案化疗序贯适形放疗治疗鼻腔NK/T细胞淋巴瘤的有效性及安全性。方法收集初治Ⅰ、Ⅱ期鼻腔NK/T细胞淋巴瘤24例,采用标准的DICE方案化疗3~4周期:异环磷酰胺1 200 mg/m2,第1~4天,静脉滴注;足叶乙甙65 mg/m2,第1~4天,静脉滴注;顺铂25 mg/m2,第1~3天,静脉滴注;地塞米松40 mg,第1~4天,静脉滴注;每21 d为1周期。化疗3~4周期后采用6MV直线加速器三维适形放疗,肿瘤剂量为46~60 Gy。评价疗效及不良反应。结果 24例患者中,总有效率为79.2%,其中完全缓解(CR)14例(58.4%),部分缓解(PR)5例(20.8%),随访1年无进展生存率(PFS)为75.0%,1年总生存率为83.3%。随访2年PFS为66.7%,2年总生存率为75.0%。毒副反应主要为化疗相关的骨髓抑制及放射性皮肤黏膜损伤。结论 DICE方案化疗序贯三维适形放疗治疗鼻腔NK/T细胞淋巴瘤有效率高,治疗相关不良反应易于控制。     

Multicenter phase II study of chemo-immunotherapy in the treatment of metastatic renal cell carcinoma

The purpose of this study was to evaluate the potential efficacy of a chemo-immunotherapy regimen for the treatment of metastatic renal cell carcinoma (MRCC). Forty-one patients with progressing MRCC and with a median age of 63 years were recruited. Planned treatment consisted of 6 courses of capecitabine 1000 mg/m twice daily on days 1 to 14 every 4 weeks, pegylated alpha-interferon 2b 50 microg every week, interleukin-2 1.8 M IU subcutaneously, and oral 13-cis-retinoic acid 0.5 mg/kg, all given 5 days/wk, 3 weeks of each month. After 6 courses of concomitant biochemotherapy, biotherapy was continued in patients who had a clinical benefit. The primary end point was response; secondary end points were the evaluation of the immunologic parameters, toxicity, progression-free, and overall survival. The treatment was well-tolerated. Grade 3 and 4 neutropenia and thrombocytopenia occurred in 5% and 7% of patients, respectively. The overall response rate in the 41 evaluable patients was 53.6% (95% confidence interval 37%-69%). Median progression-free and overall survivals were 14.7 and 27.8 months, respectively. A sustained improvement in all evaluated immunologic parameters was observed in the 36 patients treated with maintenance biotherapy. Six cycles of biochemotherapy, being followed by maintenance immunotherapy is well-tolerated and shows significant activity in patients with MRCC.     

A Phase I Clinical Trial of Irinotecan and Carboplatin in Patients with Extensive Stage Small Cell Lung Cancer

Background: Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination. Methods: Twenty patients with extensive stage SCLC received intravenous carboplatin at an area under the curve (AUC) of 5 on day 1, and irinotecan in 40-70 mg/m(2) dose levels on days 1 and 8, every 21 days, for up to 6 cycles. Results: Dose-limiting toxicity occurred in 1 patient at the 50 mg/m(2) irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m(2) (grade 5 neutropenic sepsis; combined grade 4 febrile neutropenia, grade 4 diarrhoea and grade 3 thrombosis). Toxicity patterns were consistent with the expected profile for this combination. The objective response rate was 75% and the median survival was 9.3 months (95% confidence interval 7.5-11.2). Conclusion: Irinotecan 60 mg/m(2) on days 1 and 8 combined with carboplatin AUC 5 every 21 days is recommended for phase II evaluation. This regimen has clinical activity, acceptable toxicity and greater dose intensity over those currently tested in phase III trials.     

A pilot trial of combination cisplatin, 5-fluorouracil and interferon-alpha in the treatment of advanced esophageal carcinoma

BACKGROUND/OBJECTIVES: Based on the synergistic effect between cisplatin and 5-fluorouracil (5-FU), and between 5-FU and interferon-alpha, we conducted a trial to assess the response rate and toxicity of the combination of cisplatin, 5-FU and interferon-alpha in patients with advanced esophageal cancer. METHODS: Patients with locally advanced or metastatic squamous cell or adenocarcinoma of the esophagus were eligible. No prior chemotherapy or interferon were allowed. Patients received cisplatin 80 mg/m(2) on day 1, 5-FU 750 mg/m(2)/day by continuous intravenous infusion for 5 days, and interferon-alpha 5 x 10(6) units/m(2)/day by subcutaneous injection on days 1-5 of each cycle. Cycles were repeated every 21 days for a total of 6 cycles. RESULTS: Forty patients were enrolled. Median age was 57.5 years (range 30-70). 33 had squamous carcinoma and 7 adenocarcinoma; 15 were male; the locoregional metastatic ratio was 1:39; median ECOG performance status was 2 (range 1-3). Grade 3-4 toxicities were: leukopenia (9 cases), thrombocytopenia (4), electrolyte imbalance (11), febrile neutropenia (11), vomiting (5), diarrhea (4), and mucositis (11). There were 3 early deaths, most probably related to therapy. Five patients (13%) achieved a complete response and 17 (42%) achieved a partial response, yielding an overall response rate of 55%. Response rates for squamous and adeno histology were 61% and 29%, respectively. Median survival was 6.4 months. CONCLUSION: The combination of cisplatin, 5-FU and interferon-alpha produces a high response rate in advanced squamous cell esophageal carcinoma, but with considerable toxicity. A modified combination of the above agents is presently being evaluated at our institution.