吉西他滨单药或与顺铂联合治疗胰腺癌的临床疗效评价

目的 评价吉西他滨单药以及与顺铂联合治疗局部晚期或转移性胰腺炎的疗效。临床受益反应,生存时间和毒性反应。方法 42例患者随机分为吉西他滨单药组（A组20例）和吉西他滨 顺铂联合组（B组22例）,A组;吉西他滨1000mg/m^2,每周1次,连用7周,休息1周;随后相同剂量每周1次,连用3周,休息1周,B组;吉西他滨1000mg/m^2,每周1次,连用3周,顺铂60mg/m^2,第15天给药,休息1周,每4周重复,边境用药3个周期。结果 42例患者中,可评价客观疗效者34例（A组16例,B组18例,可评价临床受益反应（CBR）者36例（A组16例,B组20例）,可进行毒性反应评估者40例（A组19例,B组21例）,A组：PR1例（6.3%)。MR4例（25.0%),SD7例（43.8%)。PD4例（25.0%)。B组;PR2例（11.0%)。MR3例（16.7%),SD8例（44.4%),PD5例（27.8%)。PR MR SD率A组为75.0%。B组为72.2%。CBR有效率A组为87.5%(14/16),B组为70.0%(14/20)。两组3个月生存率均为100%,6个月生存率分别为81.3%和61.6%。12个月生存率分别为31.3%和11.1%。B组Ⅲ、Ⅳ度血液学毒性反应发生率略高于A组,两组相比,差异无显著性。结论 吉西他滨单药以及与顺铂联合一线治疗局部晚期或转移性胰腺癌有一定的客观疗效。可明显改善患者的生活质量。延长了生存时间,患者耐受良好。     

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: This phase II study was initiated to determine the activity and toxicity of a combination of gemcitabine (GEM) and cisplatin (CDDP) in patients with pancreatic cancer. PATIENTS AND METHODS: CDDP 35 mg/m(2) was given as a 30-min infusion and GEM 1000 mg/m(2) as a 30-min infusion. Both drugs were administered once weekly for 2 consecutive weeks out of every 3 weeks to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Forty-five advanced pancreatic cancer patients received this regimen for a total of 180 cycles of chemotherapy. One complete and four partial responses have been observed for an overall response rate of 9% (95% confidence interval 10% to 11%). Twenty-one patients (46%) had stable disease and 19 progressed on therapy. The median time to progression was 3.6 months, with a median survival of 5.6 months. A clinical benefit was obtained in nine of 37 patients (24%). Side-effects were mainly represented by hematological toxicity. Grade 3/4 WHO toxicities included neutropenia (6% of the patients) and thrombocytopenia (11%). The dose of GEM and CDDP was reduced in 14 patients (31%) and treatment was delayed in 10 patients (22%). CONCLUSIONS: Our results in terms of response rate, clinical benefit and survival do not support an advantage for the combination of GEM and CDDP given by this schedule.     

Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group.

PURPOSE: In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR) combination therapy was safe and very active in patients with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients, age < or = 70 years, with stage IIIB or IV NSCLC and a performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomized to two treatment arms. Patients on arm A received CDDP 50 mg/m2, GEM 1,000 mg/m2, and VNR 25 mg/m2 on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treated with the experimental regimen to obtain a more accurate estimation of its activity rate. RESULTS: Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI , 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World Health Organization grade 3 to 4 neutropenia and thrombocytopenia occurred in 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, respectively. Severe nonhematologic toxicity was uncommon in both arms. CONCLUSION: The CDDP-GEM-VNR combination is a highly effective treatment for patients with advanced NSCLC and has a manageable toxicity. A phase III trial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway.     

A randomised phase II trial of weekly high-dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial

Previous small phase II trials have demonstrated that the combination of 5-fluorouracil (5FU) and cisplatin(CDDP) could have clinical activity in metastatic biliary tract cancer. This randomised phase II trial was designed to assess the activity and safety of a high-dose infusional weekly 5FU alone (HDFU) and the combination of 5FU, folinic acid (FA) and CDDP. Patients were included if they had histologically proven locally advanced or metastatic biliary tract carcinoma, World Health Organisation (WHO) performance status < or = 2, bilirubin <2 x upper normal limit, adequate haematological and renal functions and had not received prior chemotherapy, even in the adjuvant setting. Treatments: Arm A (HDFU) consisted of cycles of 5FU 3 g/m(2) intravenously (i.v.), 24 h infusion, weekly, for 6 weeks, followed by 1 week rest, every 7 weeks; Arm B (5FU+FA+CDDP) consisted of cycles of 5FU 2.0 g/m(2) i.v. with folinic acid 500 mg/m(2), 2 h-infusion, weekly, for 6 weeks, followed by 1 week rest plus cisplatin 50 mg/m(2), once every two weeks, for 6 weeks, followed by 1 week rest, every 7 weeks. From February 1997 to June 1999, 58 patients were randomised (29 in each arm). Patients had a median age of 58 years in Arm A and 62 years in Arm B, locally advanced disease was present in 21% of the patients in Arm A and 11% in Arm B. WHO performance status of 0/1/2 was noted in 48%/45%/7% of the patients in Arm A and 54%/43%/4% in Arm B. In both arms, the most common metastatic sites were the liver and peritoneum. Twenty-eight patients were eligible in each arm and one patient did not start the allocated therapy in Arm B. The median number of cycles was 2 [range 1-12] in Arm A and 2 [range 1-6] in Arm B. Responses for the eligible patients who started their allocated therapy were as follows: Complete Response (CR) 0% in Arm A, 4% in Arm B, Partial Response (PR) 7% in Arm A, 15% in Arm B resulting in an overall response rate [95% CI] of 7.1% in Arm A [0.9-23.5%] and 19% [6.3-38.1%] in Arm B. Disease stabilisation was observed in 46% in Arm A and 44% in Arm B. National Cancer Institute of Canada (NCIC) grade 3-4 adverse events (% of patients in Arm A/Arm B) were neutropenia 4%/26%, thrombopenia 0%/7%, stomatitis 0%/4%, vomiting 7%/14%, diarrhoea 0%/11% and neurotoxicity 4%/0%. There was one early toxic death in Arm B. The median overall survival (OS) [95% CI] was in Arm A/Arm B: 5.0 [4.0-7.4] months/8.0 [5.8-11.8] months and the median progression-free survival (PFS) was 3.3 [1.7-4.7] months/3.3 [2.3-6.7] months. Cisplatin in combination with 5FU+FA showed a higher activity than HDFU, but was more toxic. These results are not sufficient to start a phase III trial. However, our group is planning a phase III trial comparing 5FU+folinic acid versus the same schedule+oxaliplatin a platinum analogue.     

A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer

BackgroundThe contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR).MethodsTrimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5–6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used.ResultsOne hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63–NA], with median OS 45.62 months (95% CI 25.56–NA) in Arm A and 43.68 months (95% CI 27.63–NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms.ConclusionsThese data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial.Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).     

Interferon-alpha-2a with or without 13-cis retinoic acid in patients with progressive, measurable metastatic renal cell carcinoma

BACKGROUND: In patients with metastatic renal cell carcinoma (MRCC), interferon-alpha (IFN) monotherapy leads to response rates of 5-15%, dependent on the selection of patients. In 1995, preclinical and clinical data indicated an improvement of these results if IFN was combined with 13-cis retinoic acid (CRA). METHODS: In a randomized Phase II study, patients with measurable MRCC received either subcutaneous IFN (9 MU daily; Arm A) or the same daily subcutaneous dose of IFN plus oral CRA (1 mg/kg; Arm B). A central expert panel reviewed the X-ray documentation of objective responses. RESULTS: In the 50 eligible patients from Arm A, the objective, expert-reviewed response rate was 6% (95% confidence interval [95% CI], 1.3-16.6%; 2 complete responses [CRs] and 1 partial response [PR]). A 19% response rate (95% CI, 9.4-32.0%) was stated for 53 eligible patients from Arm B (2 CRs and 8 PRs). Only one of the four CRs claimed by the clinical investigator was confirmed by the central review committee. Conversely, the expert committee deemed that 3 of 12 investigator-stated PRs were CRs. Constitutional toxicity (flu-like symptoms) and/or side effects from skin, mucosa, or eyes led to discontinuation of treatment in 22% of nonprogressing patients, more often in Arm B than in Arm A. CONCLUSIONS: The results from this randomized Phase II study support expansion of the trial into a Phase III study to evaluate the effect of IFN-CRA combination therapy on the survival of patients who undergo nephrectomy prior to IFN-based immunotherapy. The considerable interobserver variability of response evaluation (individual investigator vs. expert panel) indicates the necessity of a central review of claimed responses in future Phase II studies involving patients with MRCC.     

Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma

BACKGROUND: Results from Phase II trials conducted in Asia have shown that gemcitabine alone (GEM) or with cisplatin (GC) is active among patients with metastatic or locally recurrent nasopharyngeal carcinoma (NPC). METHODS: At the Princess Margaret Hospital (PMH), Toronto, 32 patients with NPC were treated with GEM (n = 18) or GC (n = 14) from January 2000 to October 2001. Patients either received 1000 mg/m(2) GEM on Days 1, 8, and 15 every 28 days as a single agent, or with cisplatin (CG) given on day 2 at 70 mg/m(2). RESULTS: Most patients (91%) were of Southeast Asian ancestry and 29 (91%) had Type 2 (World Health Organization 1991 classification) nonkeratinizing histology. Sixteen of the GEM (89%) and five (36%) of the GC patients had received chemotherapy before entering the study. Median follow-up was 32 weeks (range, 2-97 weeks) for both groups. In the GEM group, there were five (28%) partial responses (PR) and one (6%) complete response (CR), giving an overall response rate of 34% (95% confidence interval [CI], 13.59). In the GC group, there were two (14%) CRs and seven PRs (50%), giving an overall response of 64% (95% CI, 35-87). Hematologic toxicity was dose limiting but uncomplicated. Nonhematologic toxicity included one patient with reversible reactivation of hepatitis, one with Grade 3 cisplatin-related sensory neuropathy, and three with cardiovascular events that were possibly related to chemotherapy. The median duration of response for the GEM and GC patients was 17 and 24 weeks and the 1-year survival rate was 48% (95% CI, 18-78) and 69% (95% CI, 40-99), respectively. Median survival has not been reached. CONCLUSIONS: Our study confirms that GEM is an active and tolerable drug for patients with NPC.     

A randomized trial of three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group

Survival in patients with locally advanced (stage III Mo) and metastatic (Ml) non-small-cell lung cancer (NSCLC) is short. Phase II studies have reported objective responses ranging from 20% to 60% using cisplatin-based chemotherapeutic regimens, yet few have shown improvement in median survival. In our phase II pilot studies with cisplatin (CDDP) and etoposide (VP-16), we observed a 26% response rate; with CDDP, VP-16, and mitomycin-C, a 38% response rate was obtained in advanced NSCLC patients. A total of 156 consecutive patients with locally advanced and metastatic NSCLC were randomized to one of three treatment arms to determine whether the chemotherapy protocols had any effect on response rate and median survival in a large, randomized study. Arm 1 consisted of CDDP (120 mg/m2 x 3 weeks); arm 2, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 given i.v. on days 1-3), repeated every 3 weeks; and arm 3, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 on days 1-3) given every 3 weeks, plus mitomycin C (10 mg/m2 on days 1, 21, and 42, then every 6 weeks, for a maximal dose of 100 mg). After 71 patients had been enrolled in the study, we stopped accrual in the CDDP arm due to a lack of response [1 complete response (CR) in 24 patients; 4%] and continued enrollment in the two combination-chemotherapy arms. In the CDDP/VP-16 arm a 30% response rate [1 CR, 18 partial responses (PRs)] was obtained, and in the CDDP/VP-16 mitomycin C arm a 26% response rate (4 CRs, 11 PRs) was seen among a total of 150 evaluable patients. Responses were observed in 31% of patients with favorable performance status (PS) (ECOG 0-1) vs 14% in patients with a poor PS (ECOG 2-3). Of patients with locally advanced disease (III Mo), 17 (33%) obtained an objective response, compared with 20 patients (20%) with metastatic disease. Median survival was 18 weeks in the CDDP arm, 35 weeks in the CDDP/VP-16 arm, and 37 weeks in the CDDP/VP-16/mitomycin C arm. The median survival in the multimodal chemotherapy arms was significantly greater than that obtained with CDDP alone. Toxicity was predominantly myelosuppression in the mitomycin C-containing arm (27%, wtto grade 3-4). Our study shows that combination chemotherapy using CDDP/VP-16 is active and safe in the treatment of advanced NSCLC patients with a good performance status. The addition of mitomycin C did not improve the therapeutic response.     

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of low-dose cisplatin (CDDP) and gemcitabine (GEM) in elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II trial included 46 patients aged 70 years or older with previously untreated advanced NSCLC. All patients were evaluable for response and toxicity. Treatment consisted of CDDP 50 mg/m(2) on day 1 plus GEM 1000 mg/m(2) on days 1 and 8. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 GEM-CDDP courses were administered (median 4.1 courses per patient). The chemotherapy regimen was well tolerated. No patients developed grade 4 toxicity. Grade 3 toxicities were as follows: neutropenia in six patients (13%), and anemia, thrombopenia and nausea/vomiting in one (2%) each. Two patients (4%) had mild nephrotoxicity. Of the 46 patients, 16 had a partial response (35%, 95% confidence interval, CI, 28-52%), 17 (37%) remained stable and 13 (28%) had disease progression. Eastern Cooperative Oncology Group performance status improved in 17 patients (37%), whereas 25 (54%, 95% CI 44-74%) showed a clinical benefit. Median time to progression was 20 weeks. Overall median survival was 44 weeks, with a 1-year actuarial survival rate of 35%. CONCLUSIONS: The combination of low-dose CDDP and GEM for elderly patients with advanced NSCLC is an effective and well-tolerated chemotherapeutic approach.     

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.     

Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is expected to increase due to delayed control of occupational exposure to asbestos in Japan. We investigated the use of triplet combination chemotherapy with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR) for the treatment of Japanese patients with MPM. METHODS: From December 2000 to August 2003, 12 patients received the following regimen: CDDP 40 mg/m(2), GEM 800 mg/m(2) and VNR 20 mg/m(2) on days 1 and 8 every 4 weeks. Among the 12 patients, six selected patients underwent an extrapleural pneumonectomy (EP) after a median of three cycles of triplet chemotherapy. RESULTS: The overall response rate for all patients and the response rate for chemotherapy-naive cases were 58 and 67%, respectively. The median survival time and survival rate at 2 years for all patients were 11 months and 50%, respectively. The 2-year survival rates for the patients with and without EP were 83.3 and 16.7%, respectively. CONCLUSIONS: Triplet chemotherapy with CDDP, GEM and VNR was thus found to be highly effective for patients with MPM and its toxicity was manageable. A multi-institutional phase II trial is now being planned to establish the effectiveness of this new regimen in chemotherapy-naive patients with MPM.     

吉西他滨联合顺铂治疗复发性晚期头颈部癌的临床研究

 目的 评价吉西他滨联合顺铂治疗复发性晚期头颈部肿瘤的疗效及毒副作用。方法 对复治的晚期头颈部肿瘤患者，给予GEM 1000mg／m²静滴，第1、8d，每周期CDDP 60mg／m²，静滴（分5次第1-5d），21d为1周期，2周期后评定疗效，平均3．52个周期。结果 27例可评价疗效，完全缓解1例，部分缓解7例，总有效率29．63％，中位缓解期4．4个月，中位生存期9个月。毒副作用主要为剂量限制性毒性，表现为骨髓抑制。结论 吉西他滨加顺铂可作为复发性晚期头颈部肿瘤的挽救性化疗方案。     

A randomized Phase II trial in patients with carcinoma of an unknown primary site

BACKGROUND: Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS: Patients randomized to Arm A received paclitaxel, 175 mg/m(2), intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m(2), both intravenously on Days 1-3. Patients randomized to Arm B received etoposide, 100 mg/m(2), intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. The cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS: Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19% (95% confidence interval, 4-45%) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). Hematologic toxicity on Arm B was considerable with 29% of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS: In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated.     

Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate.

PURPOSE: This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety. RESULTS: In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar. CONCLUSION: IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.     

Prolonged gemcitabine infusion in advanced non-small cell lung carcinoma: a randomized phase II study of two different schedules in combination with cisplatin

BACKGROUND: Preclinical and clinical evidence suggests that a fixed infusion rate of 10 mg/m2 per minute may be more effective than the standard 30-minute infusion of gemcitabine. To investigate the activity and toxicity of the cisplatin plus gemcitabine combination with gemcitabine at a fixed infusion rate in patients with advanced non-small cell lung carcinoma (NSCLC), the authors conducted a randomized Phase II trial of cisplatin plus gemcitabine at the 30-minute standard infusion (calibration arm) or cisplatin plus gemcitabine at a fixed infusion rate (experimental arm). METHODS: A total of 112 chemonaive patients with advanced NSCLC entered the study: 57 patients in Arm A and 55 patients in Arm B. The patients were randomly assigned to receive gemcitabine at a dose of 1000 mg/m2 on Days 1, 8, and 15 over 30 minutes (Arm A) or at a rate of 10 mg/m2 per minute (Arm B). In both treatment arms, cisplatin at a dose of 80 mg/m2 was administered on Day 15 every 28 days. RESULTS: The overall response rates in Arms A and B were 26% (95% confidence interval [95% CI], 10-42%) and 34% (95% CI, 17-52%) (intent-to-treat-analysis), respectively. The median time to disease progression was 6 months (range, 1-26 months) and 8 months (range, 2-21 months), respectively, for Arms A and B and the median overall survival was 13 months (range, 2-26 months) for each arm. It is interesting to note that a high response rate (67%) of brain metastases was noted in the experimental arm. Toxicity was tolerable and comparable in the two arms. CONCLUSIONS: The results of this randomized Phase II trial demonstrated that cisplatin plus gemcitabine with gemcitabine at fixed infusion rate (10 mg/m2 per minute) is active and well tolerated in patients with advanced NSCLC.     

A Northern California Oncology Group randomized trial of leucovorin plus 5-fluorouracil versus sequential methotrexate, 5-fluorouracil, and leucovorin in patients with advanced colorectal cancer who failed treatment with 5-fluorouracil or 5-fluorodeoxyuridine alone

The current study was initiated to confirm preliminary reports that 20% or more of patients with colorectal cancer who fail treatment with 5-fluorouracil (FUra) will respond to treatment with either leucovorin plus FUra or with sequential methotrexate, FUra, leucovorin. One hundred two patients with advanced, measureable colorectal cancer who failed treatment with FUra and/or 5-fluorodeoxyuridine (FUdR) were randomized to treatment with either high-dose leucovorin plus FUra (Arm B) or sequential methotrexate, FUra, leucovorin (Arm C). In this interim report, 92 patients were evaluable for toxicity and 89 patients were evaluable for response. Grade 3 or 4 nonhematologic toxicity which was primarily gastrointestinal was experienced by 25% of patients on both treatment arms during at least 1 treatment cycle. Hematologic toxicity was minimal. Among 43 evaluable patients on Arm B, there were 2 complete responses (5%) and 1 minor response (3%). Among 46 evaluable patients on Arm C, there was 1 complete response (2%), 1 partial response (2%), and 6 minor responses (14%). The median time to treatment failure was 2.2 months on Arm B and 3.5 months on Arm C. The median survival was 8.3 months on Arm B and 8.7 months on Arm C. Colorectal cancers that are resistant to FUra are cross-resistant to both experimental combinations.     

放射联合顺铂治疗鼻咽癌的前瞻性临床研究

９８例己确诊为鼻咽癌病例随机分为单纯放射组（４８例）和放射治疗综合应用顺铂组（５０例）。放射治疗全部采用同中心治疗，总剂量７０Ｇｙ／３５－３７次／７—８周。顺铂自放射开始后第二天使用，１次／周，２０ｍｇ／ｍ２／次。在治疗结束后三月评价，放射联合顺铂组和单纯放射组的原发肿瘤完全消退率分别为９２％和６８．７５％，颈部转移灶的完全消退率分别为９０．６％和６９．４％，两组经统计学处理均有显著性差异。随访三年（中位随访期４０月），三年生存率分别为综合治疗组８３％和单纯放射射组７６％。两组急性反应和后期反应无显著差异，所有病人均能耐受而完成治疗计划。     

Functional polymorphisms of the microsomal epoxide hydrolase gene: a reappraisal on a early-onset lung cancer patients series

As concomitant chemoradiotherapy for stage III NSCLC is associated with survival advantage in comparison to a sequential approach, we conducted a phase III randomised study aiming to determine the best sequence and safety of chemotherapy (CT) and chemoradiotherapy (CT-RT), using a regimen with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR). Unresectable stage III NSCLC patients received CDDP (60 mg/m(2)), GEM (1g/m(2), days 1 and 8) and VNR (25mg/m(2), days 1 and 8) with reduced dosage of GEM and VNR during radiotherapy (66Gy). Two cycles of CT with radiotherapy followed by two further cycles of CT alone were administered in arm A or the reverse sequence in arm B. The study was prematurely closed for poor accrual due to administrative problems. Forty-nine eligible patients were randomised. Response rates and median survival times were, respectively 57% (95% CI: 36-78%) and 17 months (95% CI: 9.3-24.6 months) in arm A and 79% (95% CI: 64-94%) and 23.9 months (95% CI: 13.3-34.5 months) in arm B (p>0.05). Chemotherapy dose-intensity was significantly reduced in arm A. Grade 3-4 oesophagitis occurred in 5 patients. One case of grade 5 radiation pneumonitis was observed. In conclusion, chemoradiotherapy with CDDP, GEM and VNR appears feasible as initial treatment or after induction chemotherapy. Consolidation chemoradiotherapy seems less toxic with a better observed response rates and survival although no valid conclusion can be drawn from the comparison of both arms.     

Comparison of cisplatin-paclitaxel combination versus cisplatin-etoposide in patients with small-cell lung cancer: a Phase III study

Cisplatin-paclitaxel and cisplatin-etoposide combination therapies were compared in limited and extensive disease in patients with small-cell lung cancer. The primary objectives were to determine median and overall survival, time to tumor progression and tolerance and the secondary objective, the response rate. From January 2003 till July 2007, 108 patients were enrolled in the study. All patients had histologically- or cytologically-confirmed small-cell lung cancer. All patients were chemotherapy and radiotherapy naive. The patients were designated to receive six cycles: in the investigational Arm A, cisplatin, 80 mg/m(2) and paclitaxel 175 mg/m(2) were infused on day 1 (1 cycle) and repeated every 3 weeks. In the control Arm B, cisplatin, 80 mg/m(2) was administered on day 1 and etoposide, 120 mg/m(2) per day was given on days 1-3 (1 cycle), every 3 weeks. In Arm A, 6 (11.3%) patients achieved a complete response and 32 (58.1%), a partial response; in Arm B, 7 (12.7%) patients achieved a complete response and 32 (58.2%) a partial response. The median survival time in Arm A patients was 12 months and in Arm B, 13 months, p=0.354. The time to tumor progression (TTP) was 8 and 6 months for Arms A and B, respectively (p=0.060). Toxicity, although common in both Arms, was acceptable. Neutropenia, anemia and diarrhea were higher in the control Arm. The cisplatin-paclitaxel combination is not superior to cisplatin-etoposide with respect to survival, TTP, toxicity and response rate. The former combination could be applied as an alternative chemotherapy regimen for patients with limited or advanced small-cell lung cancer.     

Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393.

PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) + cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended.