Phase I study of cetuximab in combination with 5-fluorouracil,mitomycin C and radiotherapy in patients with locally advanced anal cancer

Background5-fluorouracil (5FU) and mitomycin C (MMC)-based chemoradiotherapy (CRT) is standard treatment for anal squamous cell carcinoma. In this phase I study cetuximab was added and the primary aim was to determine the maximum tolerated dose (MTD) of 5FU and MMC in this combination.Methods and materialsPatients with locally advanced anal cancer, T2 (≥4 cm)–4N0–3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule.ResultsThirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46–70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3–4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%.ConclusionThe MTDs were determined as 5FU 800 mg/m² on RT days 1–4 and 29–32 and MMC 8 mg/m² on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.     

Phase II study of oral S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

Purpose

To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).

Methods and materials

S-1 (50 mg/m²) was administered orally twice daily for 14 days, with cisplatin (40 mg/m²) on days 1 and 8 of each cycle every 3 weeks, for 2–4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.

Results

Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8–97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.

Conclusions

The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.     

Pemetrexed and cisplatin in patients with advanced gastric cancer: a Korean cancer study group multicenter phase II study

BACKGROUND: Pemetrexed is a multitargeted antifolate enzyme inhibitor, which has activity against a variety of tumors, including advanced gastric cancer (AGC). The aim of this study was to assess efficacy and safety of pemetrexed plus cisplatin (PemCis) combination in the treatment of AGC in Korean patients. PATIENTS AND METHODS: This was a multicenter, single arm, open label study. Patients with no prior palliative chemotherapy received pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) day 1, every 3 weeks plus folic acid and vitamin B(12) supplementation. Response rate was assessed according to response evaluation criteria in solid tumors (RECIST) criteria. RESULTS: Of the 50 patients evaluable for efficacy, 13 had partial response for an overall response rate of 26% (95% CI, 14.6-40.3%) and 15 (30%) had stable disease. Median time to progression was 2.8 months (95%CI, 2.2-4.4 months), and median overall survival was 6.6 months (95% CI, 4.8-10.4 months). Of the 51 patients evaluable for safety, the most frequent NCI-CTC grade 3/4 toxicities were neutropenia in 49% of patients (25% of cycles) and anorexia in 10% of patients (4% of cycles). CONCLUSION: PemCis has a modest activity and acceptable toxicity profile in patients with AGC. Clinical trials with different combinations and dose regimens are, therefore, warranted.     

Multicenter phase II study of weekly paclitaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer

Purpose Since a weekly administration of paclitaxel has demonstrated a sustained efficacy and more favorable toxicity profile than a 3-weekly administration for various solid tumors, the present study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus cisplatin in patients with advanced gastric cancer. Patients and methods Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 100 mg/m² plus cisplatin 35 mg/m² on days 1 and 8 based on a 3-week cycle. Results Fifty-two patients were enrolled in the current study. Two complete responses and 17 partial responses were confirmed, giving an overall response rate of 36.5%. At a median follow-up of 8.5 months, the median time to progression and median overall survival was 6.0 and 10.8 months, respectively. Grade 3 neutropenia occurred in ten patients, while no grade 4 neutropenia or febrile neutropenia was observed. The most common non-hematologic toxicity was nausea (grade 1/2, 56.9%). There were no treatment-related deaths. Conclusion A weekly paclitaxel and cisplatin combination was found to be well-tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.     

丝裂霉素、5-氟脲嘧啶、顺铂联合治疗晚期胃癌的临床观察

目的探讨性研究晚期胃癌的姑息性联合化疗方案。方法自1992年3月至1996年12月,我们采用丝裂霉素（MMC）、5-氟脲嘧啶（5－Fu）和顺铂（DDP）联合化疗方案治疗晚期胃癌35例。结果近期总有效率（CR＋PR）为68．57％,其中CR8．57％,PR60％;中位生存时间（MST）13．5月;1、2、3、5年生存率分别为82．75％、22．85％、7．62％和7．62％。消化道反应和骨髓抑制轻微,但有一定的心脏毒性反应和相关感染发生。结论本MFP方案疗效较满意,毒副反应轻,建议在晚期胃癌患者中应用,尤以低分化腺癌者较为适用。     

Irinotecan and cisplatin with concurrent split-course radiotherapy in locally advanced nonsmall-cell lung cancer: a multiinstitutional phase 2 study

BACKGROUND: The purpose was to determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy (TRT) in locally advanced nonsmall-cell lung cancer. METHODS: Fifty patients fulfilling the following eligibility criteria were enrolled: chemotherapy-naive, good performance status (PS, 0-2), age <75, stage III, and adequate organ function. The patients received irinotecan 60 mg/m(2) intravenously on Days 1, 8, and 15, and cisplatin 80 mg/m(2) intravenously on Day 1 in the first group. The doses were reduced to 50 and 60 mg/m(2), respectively, in the second group. Two cycles of chemotherapy were repeated every 4 weeks. Split-course thoracic radiotherapy of 2 Gy/day commenced on Day 2 of each chemotherapy cycle, with 28 and 32 Gy administered in the first and second cycles, respectively. RESULTS: Fifty patients were eligible and 48 (16 in the first, 32 in the second group) patients were assessable for response, toxicity, and survival. The overall response was 83% (95% confidence interval [CI], 70%-93%). Grade 4 leukopenia, neutropenia, grade 3 or 4 diarrhea, pneumonitis, esophagitis, and fatigue occurred in 21%, 48%, 19%, 10%, and 19%, respectively. The median time to progression was 8.2 months. The median overall survival time and the 2- and 5-year survival rates were 20.1 months, 47.1%, and 17.1%, respectively. In subgroup analysis, grade 4 neutropenia, grade 3 or 4 diarrhea, the overall response, and the median survival times of the first/second groups were 63%/41%, 19%/19%, 75%/88%, and 13.1/33.4 months, respectively. CONCLUSIONS: This combined modality of irinotecan and cisplatin with concurrent TRT is active and further investigations are warranted at the second group dose level.     

奈达铂对照顺铂同步放疗治疗中晚期宫颈癌的近期疗效及安全性评价

目的 比较奈达铂或顺铂同步根治性放疗治疗局部晚期宫颈癌的疗效和安全性。方法 回顾性分析2012年1月至2014年1月63例ⅠB2～ⅣA期宫颈癌患者的临床资料,其中奈达铂同步放疗组29例,顺铂同步放疗组34例。体外照射采用三维适形放疗,总剂量50 Gy／25 f;腔内照射A点后装总剂量30 Gy。顺铂40 mg／m2静滴,放疗开始后每周1次,共6次。奈达铂40 mg／m2静滴,放疗开始后每周1次,共6次。结果 奈达铂组获CR 19例、PR 9例、PD 1例,有效率（RR）为96.5％;顺铂组获CR 28例、PR 6例,RR为100.0％,两组RR的差异无统计学意义（P＞0.05）。奈达铂组2年无复发生存率和2年无转移生存率分别为93.1％和86.2％,顺铂组分别为91.2％和88.2％,差异均无统计学意义（P＞0.05）。两组主要不良反应为白细胞减少、血小板减少、恶心呕吐和放射性肠炎。奈达铂组3～4级恶心呕吐的发生率为17.2％,顺铂组为41.1％,差异有统计学意义（P＜0.05）;其他不良反应发生率的差异均无统计学意义（P＞0.05）。结论 奈达铂同步放疗治疗中晚期宫颈癌的疗效与顺铂相似,胃肠道反应较顺铂轻,安全性良好。     

Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurrent gastric cancer

Purpose To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC). Patients and methods Cisplatin was fixed at a dose of 60 mg/m² on day 1 (D1) and the starting dose of S-1 was 60 mg/m²/day (30 mg/m² bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m² bid up to 100 mg/m²/day (level V) unless the MTD was achieved. Results Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m²/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m²/day (N = 23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). Grade 3–4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%). Conclusions The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.     

Phase I study of cisplatin and irinotecan combined with concurrent hyperfractionated accelerated thoracic radiotherapy for locally advanced non-small cell lung carcinoma

Background Irinotecan, when combined with cisplatin, is an effective treatment for advanced non-small cell lung cancer (NSCLC). This constitutes a rationale for conducting a phase I study of chemoradiotherapy including this combination for locally advanced NSCLC. Patients and methods Patients with locally advanced NSCLC and a performance status of 0 or 1 were eligible. The protocol consisted of escalating doses of irinotecan on days 1 and 15, and daily low-dose cisplatin (6 mg/m² daily for a total dose of 120 mg/m²) combined with concurrent hyperfractionated accelerated thoracic irradiation (1.5 Gy twice daily for a total dose of 60 Gy). Results The maximum tolerable dose was 50 mg/m² of irinotecan, and the dose-limiting toxicity was esophagitis. Tumor response was observed in 50% of cases, and the median survival time of the 12 patients enrolled was 10.1 months, including two patients with 5-year disease-free survival. A pharmacokinetics study demonstrated an accumulation of total platinum, but not of free platinum, during the 26-day treatment period. Conclusion The recommended dose for phase II studies was determined.     

Docetaxel and cisplatin in patients with advanced or recurrent gastric cancer: a multicenter phase I/II study

Background: Because docetaxel and cisplatin are both active against gastric cancer and have different mechanisms of action, this combination may provide additive or synergistic effects against gastric cancer. This article presents a phase I study designed to determine the recommended dose of cisplatin combined with a fixed dose of docetaxel, and a subsequent phase II study that evaluated the clinical efficacy and feasibility of this combination regimen. Methods: Patients enrolled in the study had to have histologically confirmed advanced or recurrent gastric cancer with measurable disease and adequate organ function, and to be aged 20 to 75 years, with a performance status (PS) of 0 to 2. In the phase I study, docetaxel was administered at a fixed dose of 60 mg/m² on day 1. Cisplatin was also administered on day 1, at dose levels of 60, 70, and 80 mg/m². Where dose-limiting toxicities were not observed in more than 33.3% of patients, three patients were accrued for each dose level. Results: Recommended doses for the phase II evaluation were determined to be 60 mg/m² of docetaxel and 80 mg/m² of cisplatin. Although grade 3 or more severe leukopenia and neutropenia were observed in 71.4% and 82.1% of the patients, respectively, nonhematological toxicities were not severe. The overall response rate at the recommended dose level was 25.0% (7/28 patients), and the rate was 40% (6/15) for patients with liver metastases. The median survival time was 9.7 months and the 1-year survival rate was 39.3%. Conclusion: Although this study failed to demonstrate a high response rate, this regimen was feasible and might be of value in further investigations in respect to the relatively high response rate in patients with liver metastasis and the favorable survival. Received: March 26, 2002 / Accepted: June 28, 2002 Acknowledgments We are grateful to Drs. T. Taguchi, M. Yoshida, K. Nagao, and S. Yoshida for their helpful advice and N. Hirabayashi, W. Koizumi, and K. Shirao for their extramural review during the study. Offprint requests to: Y. Mitachi     

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study

PURPOSE: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2)) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer.     

Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial.

BACKGROUND: Patients with advanced biliary tract carcinoma face a particularly dismal prognosis, and no standard palliative chemotherapy has yet been defined. Among several different single agents, mitomycin C and, more recently, the oral fluoropyrimidine capecitabine and the nucleoside analogue gemcitabine, have been reported to exert antitumour activity. In view of a potential drug synergy, the present randomised phase II trial was initiated. The aim was to investigate the therapeutic efficacy and tolerance of mitomycin C (MMC) in combination with gemcitabine (GEM) or capecitabine (CAPE) in previously untreated patients with advanced biliary tract cancer. PATIENTS AND METHODS: A total of 51 patients were entered in this study and randomly allocated to treatment with MMC 8 mg/m2 on day 1 in combination with GEM 2000 mg/m2 on days 1 and 15 every 4 weeks, or MMC 8 mg/m2 on day 1 plus CAPE 2000 mg/m2/day on days 1-14, every 4 weeks. In both arms, chemotherapy was administered for a total of 6 months unless progressive disease occurred earlier. RESULTS: Pretreatment characteristics were well balanced between the two treatment arms. The overall independent review committee-confirmed response rate among those treated with MMC + GEM was 20% (five of 25) compared with 31% (eight of 26) among those treated with MMC + CAPE. Similarly, median progression-free survival (PFS; 4.2 versus 5.3 months) and median overall survival (OS; 6.7 versus 9.25 months) tended to be superior in the latter combination arm. Chemotherapy was fairly well tolerated in both arms, with a comparably low rate of only grade 1 and 2 non-haematological adverse reactions. Also, only four (17%) patients in both treatment arms experienced grade 3 leukocytopenia, and three (13%) and four (17%) had grade 3 thrombocytopenia in the MMC + GEM and MMC + CAPE arm, respectively. CONCLUSIONS: The results of this study indicate that both combination regimens are feasible, tolerable and clinically active. The MMC + CAPE arm, however, seems to be superior in terms of response rate, PFS and OS, and should therefore be selected for further clinical investigation in advanced biliary tract cancer.     

NP方案序贯放疗治疗局部晚期非小细胞肺癌临床疗效观察

目的 :观察国产去甲长春花碱 (盖诺 )联合顺铂序贯放疗治疗局部晚期非小细胞肺癌的疗效和不良反应。方法 :31例Ⅲ期非小细胞肺癌首先接受NP方案化疗 ,即 :盖诺 2 5mg/m2 ,d1、d8,顺铂 2 5mg/m2 ,d1～ 3,2 1天为 1个周期 ,至少 3个周期化疗后又随机分为常规放疗组 (A组 )及常规放疗加分次立体定向放疗组 (B组 )。结果 :化疗总有效率 4 5 1% ,化疗 +放疗总有效率 6 7 7%。A和B组有效率分别为 5 0 0 % (8/16 )和 86 6 % (13/15 ) (P <0 0 5 ) ;1年生存率分别为 5 6 2 % (9/16 )和 6 6 6 % (10 /15 ) ;中位生存期 (MST)各为 13 2和 16个月 ;中位疾病进展时间 (TTP)各为 7 1个月和 8 3个月。全组毒副反应有白细胞减少、贫血、静脉炎、食管炎和肺炎。结论 :NP方案序贯放疗治疗局部晚期非小细胞肺癌疗效明显 ,耐受性好。     

Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: Results from a British Thoracic Oncology Group randomised phase III trial

BackgroundPlatinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.MethodsThe three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m² on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m² (GC80) or cisplatin 50 mg/m² (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).FindingsThe trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99–1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08–1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3–4 compared to 43% GC80 and 30% GC50).InterpretationIn combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m² in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m² has worse survival which is not compensated by better quality of life.ClinicalTrials.gov identifierNCT00112710.EudraCT Number2004-003868-30.Cancer Research UK trial identifierCRUK/04/009.     

Phase II study of preoperative paclitaxel/cisplatin with radiotherapy in locally advanced esophageal cancer

PURPOSE: Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival. METHODS AND MATERIALS: Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m2 on Day 1 and 5-fluorouracil 350 mg/m2 and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy. RESULTS: Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p < 0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%. CONCLUSION: Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.     

Concurrent chemoradiotherapy for locally advanced and metastatic esophageal cancer: longterm results of a phase II study of UFT/CDDP with radiotherapy

Background. No effective treatment for advanced esophageal cancer extending to adjacent organs or associated with distant metastasis is known. We prospectively analyzed the efficacy of concurrent chemoradiotherapy with uracil plus tegafur (UFT) and cisplatin (CDDP) for such cases of advanced esophageal cancer. Methods. Patients with advanced cancers received 60 to 70Gy of radiotherapy given during a period of 7 weeks, concurrently with daily oral UFT (200mg/m² per day), and a 24-h infusion of CDDP (70mg/m²) on days 8 and 36. After chemoradiotherapy, UFT (250mg/m²/per day) was administered daily for 1 year, while CDDP (80mg/m²) was administered twice every 4 weeks. Results. Patients with stage III disease numbered 31, while 24 had stage IV disease according to the tumor-node-metastasis (TNM) staging. Including all patients, complete response (CR) occurred in 20% and partial response (PR) in 51%. In stage III patients, CR, PR, and CR+PR rates were 29%, 48%, and 77%, respectively. In stage IV patients, CR, PR, and CR+PR rates were 8%, 54%, and 63%. Grade 4 leukocytopenia occurred in 22% of patients, and grade 3 pain, nausea/vomiting, and oral mucositis occurred in 7%, 9%, and 4% of patients respectively, but resolved after the reduction or discontinuation of chemoradiotherapy. Median survival in stage III patients was 415 days (range, 3 to 3046 days), and in stage IV patients, it was 187 days (range, 75 to 764 days). The 2-year survival rate in stage III patients was 25% and it was 4% in stage IV patients. The 5-year survival rate in stage III patients was 7%, while in stage IV patients it was 0%. Conclusion. This combined treatment may be a promising nonsurgical management option for locally advanced esophageal cancer, and can achieve good palliative effects in patients with distant metastasis.     

A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer

PURPOSE: In vitro studies suggest that low-dose gemcitabine sensitizes cells to radiation therapy and that this effect persists for 48 h after drug exposure. Cisplatin is a radiation sensitizer and is also synergistic with gemcitabine in some in vitro tumor systems. Gemcitabine's radiosensitizing properties can theoretically be exploited by twice-weekly administration. This study assessed toxicity in patients with pancreatic cancer treated with radiation therapy, gemcitabine, and cisplatin. METHODS AND MATERIALS: Patients with locally advanced pancreatic or gastric cancer were eligible. Gemcitabine and cisplatin were given twice weekly for 3 weeks during radiation therapy (50.4 Gy in 28 fractions). The starting dose of gemcitabine was 5 mg/m(2) i.v. The starting dose for cisplatin was 5 mg/m(2). Chemotherapy doses escalated every 3 to 6 patients according to a standard Phase I study design. RESULTS: Twenty-four evaluable patients, all with pancreatic cancer, were treated on this protocol. Grade 3 neutropenia occurred in 2 patients, Grade 3 thrombocytopenia occurred in 2, and Grade 4 lymphopenia occurred in 1. There was no clear relationship between chemotherapy dose and hematologic toxicity. The most common Grade 3-4 nonhematologic toxic responses were vomiting (7 patients) and nausea (7 patients). Dose-limiting toxicity consisting of Grade 4 nausea and vomiting occurred in 2 of 3 patients at dose Level 6 (gemcitabine 45 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.) without dose-limiting toxicity. CONCLUSION: Gemcitabine 30 mg/m(2) i.v. twice weekly and cisplatin 10 mg/m(2) i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity.     

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer

Aims: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42–75 years) were enrolled. Both cisplatin (40 mg/m²) and vinorelbine (20 mg/m²) were given on days 1 and 8 every 3 weeks. Beginning on day 2 of chemotherapy, thoracic radiotherapy was given for approximately 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results: Five of the 26 patients achieved a complete response, and 16 achieved a partial response for an overall response rate of 80.8% (95% confidence interval, 60.6–93.4%). The median survival time was 23 months (range, 4–43 months). Overall survival rates at 1 and 2 years were 80 and 56%, respectively. Hematologic toxicities included grade 3–4 neutropenia in 84.6% of patients, grade 3–4 thrombocytopenia in 3.8%, and grade 3–4 anemia in 61.5%. Two patients (7.7%) had grade 3 radiation esophagitis that resolved completely without dilation. Grade 3–4 radiation pneumonitis occurred in two patients (7.7%) and was treated with corticosteroids. Both patients had a good partial resolution of symptoms and radiographic abnormalities. There were no treatment-related deaths. The actual delivered dose intensities for both cisplatin and vinorelbine were 79.5%. Radiotherapy was completed in 96% of patients. Conclusion: Concurrent chemoradiotherapy with cisplatin and vinorelbine administered on a divided schedule is effective and well tolerated in patients with locally advanced NSCLC.