Phase II study of a three-drug combination of ifosfamide, cisplatin and vindesine in non-small-cell lung cancer

Between February 1986 and April 1987, we conducted a phase II clinical trial of a three-drug combination of ifosfamide, cisplatin, and vindesine in advanced non-small-cell lung cancer. The combination consisted of ifosfamide, 1,300 mg/m2, on days 1 through 5, cisplatin, 20 mg/m2, on days 1 through 5, and vindesine, 3 mg/m2, on days 1 and 8. Courses were repeated at 4-week intervals until disease progression or unacceptable toxicity occurred. Of 21 patients evaluated, one had a complete response and 12 had partial response, with an overall response rate of 62%. The projected median response duration was 30 weeks. The median survival for all patients has not been reached: 14 of 21 patients are still alive with a median follow-up period of 41 weeks (range, 12 to 73 weeks). The major toxicity was myelosuppression. One patient died of septicemia while neutropenic, but the toxicity was well tolerated in the rest. These results indicate that this three-drug combination is active against non-small-cell lung cancer and warrants further clinical trials.     

长春瑞滨联合奥沙利铂治疗老年晚期非小细胞肺癌

目的:评价长春瑞滨(NVB)联合奥沙利铂(OXA)治疗老年晚期非小细胞肺癌的疗效和毒副反应。方法:对住院治疗的老年晚期肺癌患者28例,用NVB联合OXA方案化疗,NVB25mg/m2ivd1、8,OXA130mg/m2ivd1,4周重复。结果:全组28例共完成78周期化疗,PR11例,有效率39.29%,中位生存期10.3个月,1年生存率32.14%,主要毒副反应为骨髓抑制和周围神经炎。结论:长春瑞滨联合奥沙利铂治疗老年晚期非小细胞肺癌有较好疗效,毒副反应可以耐受。     

Phase II study of radiotherapy with three-dimensional conformal boost concurrent with paclitaxel and cisplatin for Stage IIIB non-small-cell lung cancer

PURPOSE: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy with paclitaxel/cisplatin for Stage IIIB locally advanced non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Radiotherapy was administered to a total dose of 70.2 Gy (daily fraction of 1.8 Gy, 5 days/wk), over an 8-week period, combined with chemotherapy. The chemotherapy consisted of weekly 40 mg/m2 of paclitaxel plus 20 mg/m2 of cisplatin for 8 consecutive weeks. All patients received three-dimensional conformal radiotherapy (3D-CRT), based on computed tomography simulated planning after 41.4 Gy. The median follow-up period of survivors was 24 months. RESULTS: Between January 2000 and October 2002, 135 patients with a median age of 60 years were enrolled and analyzed in this prospective trial. The overall response rate was 75% including 2 cases of complete response. The major patterns of failure were local failure and distant metastasis. The 2-year overall and progression-free survival rates were 37% and 18%, respectively. The median overall and progression-free survival times were 17 months and 9 months, respectively. Hematologic toxicity >Grade 2 was observed in 19% of patients and severe non-hematologic toxicity was infrequent. CONCLUSIONS: Three-dimensional conformal radiotherapy, combined with paclitaxel and cisplatin chemotherapy, was associated with a satisfactory outcome with manageable toxicity. Further investigations are needed to improve the local control.     

A phase II trial of vinorelbine and cisplatin in previously untreated inoperable non--small-cell lung cancer

Weekly vinorelbine injection with cisplatin had been used in treatment of non-small-cell lung cancer. We performed a phase II trial to evaluate the efficacy and toxicity of a new schedule of vinorelbine and cisplatin in patients with previously untreated, inoperable (stage IIIB or stage IV) non-small-cell lung cancer. From April 1996 to May 1997, 52 patients were enrolled for study, and 50 patients were eligible and evaluable for both response and toxicity assessment. Therapy consisted of vinorelbine, 30 mg/m2, intravenously on days 1 and 5 of a 21-day cycle, and cisplatin 100 mg/m2 (reduced to 80 mg/m2 after the first seven patients) given on day 1. A total of 211 treatment courses were administered; the median number of cycles administered per patient was 4.5 (range: 1-6), the median dose intensity for vinorelbine was 16.9 mg/m2/week (84.4%), whereas that of cisplatin was 22.8 mg/m2/week (84.7%). Twenty-five patients responded to therapy for an overall response rate of 50%; one patient attained a complete response (2%). The main toxicities were vomiting, myelosuppression, and diarrhea, which included World Health Organization grade 3 or 4 nausea/vomiting (58% patients), anemia (41% patients), neutropenia (12% patients), and diarrhea (14%). The median duration of responses was 9 months. The median time to disease progression was 6.8 months (range 0.4-18.1 months). Median survival was 13 months, and 54% of patients were alive at 1 year. We conclude that this new schedule of vinorelbine and cisplatin achieves a high response with acceptable toxicity profile in patients with advanced non-small-cell lung cancer.     

Phase I study of acivicin and cisplatin in non-small-cell lung cancer. A National Cancer Institute of Canada study

Seventeen previously untreated patients with metastatic non-small-cell lung cancer were entered in this phase I trial. Treatment consisted of a combination of acivicin and cisplatin at a starting dose of 12 and 15 mg/m2, respectively, given i.v. during 5 days and repeated every 28 days. A total of 46 cycles was given. Renal function abnormality was the dose-limiting toxicity of cisplatin with a maximum tolerated dose of 12 mg/m2. This toxicity occurred at a dose lower than expected, indicating a possible potentiation of platinum renal toxicity by acivicin. Myelosuppression was the dose-limiting toxicity of acivicin, with a maximum tolerated dose of 12 mg/m2. Other side effects included generalized weakness and gastrointestinal and neurological symptoms. In 15 patients evaluable for response seven progressed, six were stable for a median duration of 13 weeks, and two patients achieved a partial remission lasting 8 and 24 weeks, respectively. The overall response rate was 13%. The recommended phase II dose of both agents in this schedule was 12 mg/m2. The possible enhancement of cisplatin toxicity might have compromised the overall response rate of the combination and further studies using these drugs in this schedule are not recommended.     

Vinorelbine plus low-dose cisplatinum with concomitant radiotherapy for the treatment of locally advanced or inoperable non-metastasized non-small-cell lung cancer (stage I-IIIB): a phase II study.

In a phase II study, we assessed the toxicity and efficacy of daily low-dose cisplatin (6 mg/m2) and weekly vinorelbine (15 mg/m2) with concurrent thoracic irradiation (60 Gy) for locally advanced non-metastasized non-small-cell lung cancer. The overall response rate was 65%, complete response 12% and the median overall survival was 64 weeks.     

低剂量持续静脉滴注吉西他滨一线治疗晚期非小细胞肺癌的临床研究

背景与目的:目前已将吉西他滨联合顺铂作为晚期非小细胞肺癌的一线化疗方案,吉西他滨的常规使用剂量和方法是1000mg/m2半小时静脉滴注,第1、8天,每3周为一个疗程。本研究旨在评价低剂量吉西他滨持续6h静脉滴注联合顺铂一线治疗晚期非小细胞肺癌的有效性和安全性。方法:48例经病理和/或细胞学检查确诊、未经化疗的晚期非小细胞肺癌患者,采用吉西他滨250mg/m2持续静脉滴注6h,第1、8天,顺铂75mg/m2,每3周为一疗程,连续使用2疗程以上。结果:48例患者中46例可评价疗效,所有患者可评价不良反应。完全缓解率2.2%,部分缓解率30.3%,总有效率为32.5%,中位治疗至进展时间为5.1个月,中位生存时间为10.2个月,1年生存率36.6%。白细胞减少发生率为60.4%,血小板减少发生率为39.5%,Ⅲ～Ⅳ度的白细胞和血小板减少发生率分别为20.8%和12.5%。结论:低剂量吉西他滨持续6h静脉滴注联合顺铂一线治疗晚期非小细胞肺癌疗效确切、不良反应轻。     

The role of combination cyclophosphamide, doxorubicin and cisplatin (CAP) chemotherapy in advanced non-small-cell lung cancer

Thirty-one patients with non-small-cell lung cancer (NSCLC), stage III (T3 N2 M 0-1), were treated with cyclophosphamide (400 mg/m2), adriamycin (40 mg/m2) and cisplatin (60 mg/m2) (CAP) every 4 weeks for 8 cycles. Twenty-six patients were evaluable for response. Patients characteristics included: median age, 63 years; median performance status, 70% (range 60%-100%). One hundred and fifty-five cycles of chemotherapy were administered with a median of 5. There were 9 partial responses and 3 complete remissions, for an overall response rate of 46%. The median survival duration was 9 months, and 29% survived 1 year. CAP combination chemotherapy was well tolerated without nephrotoxicity, which can be imputed to the strong saline hydration given. Seventy percent of the patients did not experience emesis due to the antiemetic regimen used.     

Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan.

BACKGROUND: To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan (IP) in patients with untreated advanced non-small-cell lung cancer (NSCLC) by a non-inferiority design. PATIENTS AND METHODS: A total of 602 patients were randomly assigned to one of four regimens: cisplatin 80 mg/m(2) on day 1 plus irinotecan 60 mg/m(2) on days 1, 8, 15 every 4 weeks (IP) carboplatin AUC 6.0 min x mg/mL (area under the concentration-time curve) on day 1 plus paclitaxel 200 mg/m(2) on day 1 every 3 weeks (TC); cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1000 mg/m(2) on days 1, 8 every 3 weeks (GP); and cisplatin 80 mg/m(2) on day 1 plus vinorelbine 25 mg/m(2) on days 1, 8 every 3 weeks (NP). RESULTS: The response rate, median survival time, and 1-year survival rate were 31.0%, 13.9 months, 59.2%, respectively, in IP; 32.4%, 12.3 months, 51.0% in TC; 30.1%, 14.0 months, 59.6% in GP; and 33.1%, 11.4 months, 48.3% in NP. No statistically significant differences were found in response rate or overall survival, but the non-inferiority of none of the experimental regimens could be confirmed. All the four regimens were well tolerated. CONCLUSION: The four regimens have similar efficacy and different toxicity profiles, and they can be used to treat advanced NSCLC patients.     

S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks. RESULTS: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34-61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%). CONCLUSIONS: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.     

Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data.

PURPOSE: High-dose adjuvant interferon alpha-2b (IFN alpha 2b) for high-risk melanoma is a 1-year regimen that improves relapse-free and overall survival but has significant toxicity. A quality-of-life--adjusted survival (QAS) analysis analysis of two cooperative group phase III trials, E1684 and E1690/S9111/C9190, was performed, incorporating patient values (utilities) for the toxicity of IFN alpha 2b treatment and melanoma recurrence. PATIENTS AND METHODS: Quality-Adjusted Time Without Symptoms or Toxicity methodology was used with melanoma patient utilities and trial data to estimate the effect of IFN alpha 2b on QAS. The increase or decrease in QAS that patients could expect from treatment was estimated based on their utilities. Eleven utility predictor questions were tested to identify patients with utilities that result in decreased QAS. RESULTS: Using E1684 data, IFN alpha 2b would result in an increase in QAS for all sets of patient utilities. This benefit was significant (P <.05) for 16% of patients. Using E1690/S9111/C9190 data, 77% of patients would experience a benefit in QAS from IFN alpha 2b and 23% would experience a decrease in QAS; neither of these effects was statistically significant. Using utility predictors and the E1690/S9111/C9190 analysis, a decision rule was formulated that helps identify patients in whom IFN alpha 2b may detract from QAS. CONCLUSION: Most patients experienced improvement in QAS in both trials, but this benefit was statistically significant in only 16% of patients in E1684. Change in QAS depends more on the utility for IFN alpha 2b toxicity than on the utility for melanoma recurrence. Cancer patients probably have higher utilities for IFN alpha 2b toxicity than members of the general population and will tend to favor IFN alpha 2b treatment as a result.     

Recombinant alpha-interferon and vinblastine in metastatic renal cell carcinoma: efficacy of low doses

Twenty-six patients with metastatic renal cell carcinoma (RCC) were treated in a phase I-II trial with recombinant interferon alpha-2b (alpha-IFN) and vinblastine (VBL) in combination. Patients received IFN at a starting dose of 3 x 10(6) IU/m2 subcutaneously three times a week and VBL 0.1 mg/kg intravenously every 3 weeks, with dose modification for toxicity. All patients were evaluable for toxicity; 18 patients were evaluable for efficacy. An objective response rate of 44% was observed (eight of 18 patients, with one complete response and seven partial responses). The median duration of response was 5 months. The actuarial survival of responding patients was significantly longer than that of nonresponding patients. In general, the toxicity was tolerable; the subjective toxicity and fever were similar to that reported for the same doses of IFN alone. Only a mild neurotoxicity, usually mixed polyneuropathy, occurred with increased frequency. Alpha-IFN and VBL administered at low doses in combination demonstrated the highest response rate so far reported in RCC without significant toxicity.     

Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration

Ninety-seven patients with recurrent or metastatic renal cell carcinoma were randomized to receive recombinant interferon (IFN) alfa-2b (Intron A; Schering-Plough, Kenilworth, NJ) by either the subcutaneous (SC) or intravenous (IV) route. The SC dosage was 2 X 10(6) IU/m2 three times weekly, and the IV dose 30 X 10(6) IU/m2 for five consecutive days every 3 weeks. Dose escalation to a maximum of 10 X 10(6) IU/m2 SC and 50 X 10(6) IU/m2 IV was allowed for patients with minimal or absent toxicity. Five of 51 of the SC-treated patients (10%) and three of 46 of the IV-treated patients (7%) had a partial response (PR) or complete response (CR). Patients with prior nephrectomy, no prior treatment, and lack of bone metastases were most likely to respond, and a retrospective analysis of this subgroup revealed a 23% response rate. Achievement of response took from 3 weeks to 11 months, while response duration lasted from 3 to 31+ months. All responders had prior nephrectomy; six of eight had no prior chemotherapy or hormonal therapy; five had lung metastases, and none had bone metastases. Regardless of route, almost all patients developed a flu-like syndrome; however, grade 3 or greater toxicity was much more common for IV-treated patients. This trial demonstrates modest, but definite antitumor activity for recombinant interferon in advanced renal cell carcinoma. SC administration with lower dose and toxicity is as effective as treatment administered IV.     

Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group

BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.     

Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003.

PURPOSE: Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Of 396 patients registered, 367 eligible patients were randomly assigned to either arm 1 (n = 181), which consisted of treatment every 21 days with paclitaxel 225 mg/m2/3 h, carboplatin (area under the curve = 6), and tirapazamine 260 mg/m2 in cycle 1 (which was escalated, if tolerable, to 330 mg/m(2) in cycle 2), or arm 2 (n = 186), which consisted of paclitaxel and carboplatin as in arm 1 with no tirapazamine. RESULTS: Patient characteristics were similar between the two arms. There were no statistically significant differences in response rates, progression-free survival, or overall survival. Patients on arm 1 had significantly (P < .05) more abdominal cramps, fatigue, transient hearing loss, febrile neutropenia, hypotension, myalgias, and skin rash and were removed from treatment more often as a result of toxicity than patients in arm 2 (26% v 13%, respectively; P = .003). More than 40% of patients did not have the tirapazamine dose escalated, primarily because of toxicity. The trial was closed early after an interim analysis demonstrated that the projected 37.5% improvement in survival (8 v 11 months median survival) in arm 1 was unachievable (P = .003). CONCLUSION: The addition of tirapazamine to paclitaxel and carboplatin does not result in improved survival in advanced NSCLC compared with paclitaxel and carboplatin alone but substantially increases toxicity.     

Japanese experience with second-line chemotherapy with low-dose (60 mg/m2) docetaxel in patients with advanced non-small-cell lung cancer

PURPOSE: To assess the efficacy and toxicity of relatively low-dose docetaxel (60 mg/m2) for previously treated advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIA-IV) NSCLC who had previously undergone at least one series of chemotherapy were enrolled. Previous paclitaxel use was allowed, but docetaxel was not. Docetaxel was administered at an initial dose of 60 mg/m2 intravenously on day 1 over 90 min every 3 weeks. RESULTS: From June 1997 to November 1999, 22 patients were entered into this study. The total number of cycles delivered to 22 patients was 53, with a median per patient of 2. Four patients achieved a partial response (PR), and the overall response rate was 18.2% (95% confidence interval 5.1-40.3%). The median time to progression was 13.7 weeks. The median survival time was 7.8 months, and the 1-year survival rate was 25%. About 73% of patients experienced grade 3 or 4 neutropenia. Neutropenic fever was observed in four patients (18%). Non-hematologic toxicities were generally mild. No treatment-related deaths occurred. CONCLUSIONS: Although the validity of the results of this study is limited due to the small and monoracial study population examined, low-dose (60 mg/m2) docetaxel for previously treated advanced NSCLC appears to yield antitumor activity and survival benefit comparable to those obtained with the conventional dose (100 mg/m2).     

Phase II study of docetaxel and carboplatin as second-line treatment in NSCLC

Aim of this study was to evaluate activity and toxicity of docetaxel and carboplatin as second-line treatment in advanced non-small-cell lung cancer (NSCLC) patients who failed or relapsed after previous chemotherapy. Patients had to have unresectable stage IIIb or IV NSCLC, previous chemotherapy, a performance status < or = 2, a normal bone marrow reserve, and an adequate renal and liver function. Treatment consisted of docetaxel 75 mg/m2 and carboplatin AUC 6 mg/ml min administered every 3 weeks for a maximum of 5 cycles. Fifty-seven patients with a median age of 57 years were included. Prior treatment consisted of gemcitabine alone (n = 2) or gemcitabine in combination with cisplatin (n = 26) or epirubicin (n = 29). Median number of cycles for carboplatin and docetaxel was 4. Granulocytopenia and thrombocytopenia common toxicity criteria (CTC) grades 3 and 4 occurred in 79 and 30% of patients, respectively. Febrile neutropenia occurred in eight patients (14%), of whom two patients died. Fatigue grades 2 and 3 occurred in 42% of patients. Other non-haematological toxicity was mild. Tumour response rate was 37%, irrespective of the previous regimen. Median survival was 31 weeks, 1-year survival was 32%. In conclusion, the combination of docetaxel and carboplatin is active as second-line treatment in platinum and non-platinum pre-treated patients.     

A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.

BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.     

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

Dose-escalation study was performed to evaluate the maximum tolerated dose, recommended dose and toxicity profile of weekly irinotecan with daily carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Thirty-one previously untreated patients with unresectable stage III non-small-cell lung cancer were enrolled in this study. Patients received weekly irinotecan plus carboplatin (20 mg x m(-2) daily for 5 days a week) for 4 weeks and thoracic radiotherapy (60 Gy in 30 fractions). The irinotecan dose was escalated from 30 mg x m(-2) in increments of 10 mg x m(-2). Four irinotecan dose levels were given and 30 patients were assessable. Their median age was 62 years (range: 52-72 years), 28 had a performance status of 0-1 and two had a performance status of 2, 12 had stage IIIA disease and 18 had IIIB disease. There were 19 squamous cell carcinomas, 10 adenocarcinomas, and one large cell carcinoma. The dose-limiting toxicities were pneumonitis, esophagitis, thrombocytopenia and neutropenia. The maximum tolerated dose of irinotecan was 60 mg x m(-2), with two patients developing grade 4 pulmonary toxicity and one patient died of pneumonitis (grade 5). The recommended dose of irinotecan was 50 mg x m(-2). Other grade 3 or 4 toxicities were nausea and vomiting. Three patients achieved complete remission and 15 had partial remission, for an objective response rate of 60.0%. The median survival time was 14.9 months, and the 1- and 2-year survival rates were 51.6% and 34.2%, respectively. The study concluded that the major toxicity of this regimen was pneumonitis. This therapy may be active against unresectable non-small-cell lung cancer and a phase II study is warranted.     

伊立替康或奥沙利铂联合卡培他滨治疗晚期胃癌的疗效比较

目的 观察并比较伊立替康(CPT-11)联合卡培他滨(CAP)与奥沙利铂(L-OHP)联合CAP治疗晚期胃癌的近期疗效和毒副反应.方法 将63例晚期胃癌患者随机分为两组,CPT-11+CAP组32例,应用CPT-11联合CAP方案治疗;L-OHP+CAP组31例,应用L-OHP联合CAP方案治疗.2个周期后评价疗效及毒副反应,有效病例4周后进行疗效确认.结果 CPT-11+CAP组PR 13例,有效率为40.6%,中位无进展生存期为6.3个月.L-OHP+CAP组PR 12例,有效率为38.7%,中位无进展生存期为6.1个月.两组有效率及中位无进展生存期比较,差异均无统计学意义(P＞0.05).两组的主要毒副反应为胃肠道反应、周围神经毒性和骨髓抑制.CPT-11+CAP组Ⅲ、Ⅳ度腹泻的发生率(28.1%)高于L-OHP+CAP组(3.2%,P=0.018),Ⅲ、Ⅳ度周围神经毒性的发生率(3.1%)低于L-OHP+CAP组(25.8%,P=0.027).两组均无化疗相关性死亡.结论 CPT-11联合CAP方案与L-OHP联合CAP方案对晚期胃癌均有较好的疗效,毒副反应均可耐受.

Abstract：

Objective To observe and compare the response rate and toxicity of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer.Methods Sixty-three patients with advanced gastric cancer were randomly divided into two groups.The CPT-11 + CAP group consisted of 32 patients who received irinotecan plus capocitabine: CPT-11 100 mg/m2 was injected in 90 minutes on d 1,8 ;capecitabine 2000 mg/m2, bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repoated for every 21 days.The L-OHP + CAP group consisted of 31 patients who received oxaliplatin plus capecitabine: oxaliplatin 100 mg/m2 on day 1, capocitabine 2000 mg/m2, bid,with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days.Two or more cycle chemotherapy was completed in each group.Results In the CPT-11 + CAP group, no patient achieved complete response and 13 patients achieved partial response.The overall response rate was 40.6% (13/32), and the median progression-free survival time was 6.3 months.In the L-OHP + CAP group, no patient achieved complete response and 12 patients achieved partial response.The overall response rate was 38.7% (12./31), and the median progression-free survival time was 6.1 months.There was no significant difference between them (P ＞ 0.05 ).The most common toxicities were gastrointestinal reaction,peripheral neuropathy and myelosuppression in the two groups.Patients in CPT-11 + CAP group experienced more Ⅲ/Ⅳ diarrhea (28.1%/3.2%, P =0.018).On the contrary, the rate of Ⅲ/Ⅳ neurotoxicity in the group B was higher (25.8%/3.1%, P = 0.027).No chemotherapy-related death occurred.Conclusion The therapeutic effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer are good and comparable, and their toxicities are tolerable.