Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.     

Phase I study of hypofractionated dose-escalated thoracic radiotherapy for limited-stage small-cell lung cancer

PURPOSE: To determine the maximal tolerated dose of hypofractionated thoracic radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer patients. METHODS AND MATERIALS: Three radiotherapy regimens were used. Radiotherapy was given in two phases: patients initially received 20 Gy in 10 fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned with conformal techniques. All patients received four cycles of cisplatin (25 mg/m2) and etoposide (100 mg/m2) chemotherapy. Radiotherapy commenced with Day 1 of Cycle 2 of chemotherapy. All complete/near-complete responders were offered prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was based on the dose that caused unacceptably high rates of radiotherapy-related toxicity. RESULTS: Thirteen patients were accrued. All patients who commenced radiotherapy received all prescribed chemo- and radiotherapy. There were no treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3 esophagitis. With a median follow-up of 7 months, median overall survival was 9.5 months. CONCLUSIONS: The maximal tolerated dose of thoracic radiotherapy with concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.     

Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial

BACKGROUND: A modified Phase I trial was conducted evaluating the incorporation of 3-dimensional conformal radiation therapy (3DCRT) into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III, unresectable nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was performed. Endpoints included response rate, toxicity, and survival. METHODS: Twenty-nine patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (AUC 6) and paclitaxel (225 mg/m(2)/3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC 2) and paclitaxel (45 mg/m(2)/3 hours) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts. RESULTS: The response rate to induction carboplatin/paclitaxel was 52%. Three patients (10%) experienced disease progression during the induction phase. No dose-limiting toxicity was seen during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, with 18% of patients developing Radiation Therapy Oncology Group Grade 3 esophagitis. The overall response rate was 70% (1 complete response and 18 partial responses). Survival rates at 1 and 2 years were 69% and 45%, with a median survival of 21 months. The 1-year progression free survival probability was 41% (95% confidence interval, 23-59%). CONCLUSIONS: Incorporation of 3DCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Accrual is continuing in a Phase II fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel.     

Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified phase I/II trial

BACKGROUND: A modified Phase I/II trial was conducted evaluating the incorporation of three-dimensional conformal radiation therapy into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III unresectable nonsmall cell lung carcinoma (NSCLC). The dose of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints included response rate, toxicity, and survival. METHODS: Sixty-two patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (area under the concentration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x 6) carboplatin (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS: The response rate to induction carboplatin/paclitaxel was 40%. Eight patients (13%) progressed on the induction phase. No dose-limiting toxicity was observed during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, however, only 8% developed Grade 3/4 esophagitis using Radiation Therapy Oncology Group criteria. The overall response rate was 52%. Survival rates at 1, 2, 3, and 4 years were 71%, 52%, 40%, and 36%, respectively, with a median survival of 26 months. The 1-, 2-, and 3-year progression free survival probabilities were 47%, 35%, and 29%, respectively. CONCLUSIONS: Incorporation of TCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Both locoregional and distant failure remain problematic in this population of patients.     

A Phase I Trial of Combination Chemotherapy Employing Carboplatin, Vinca Alkaloids, with or without Bleomycin in Patients with Advanced Malignant Tumors

A Phase I trial of three carboplatin-based combination chemotherapy regimens was conducted. These included: carboplatin plus vindesine; carboplatin, vindesine, plus bleomycin; and, carboplatin plus vinblastine. Carboplatin was administered every 28 days as an intravenous bolus. The initial dose was 150 mg/m² and doses were escalated by 50 mg/m² in each successive group of patients. Vindesine was given at a dose of 3 mg/m² weekly for 5 doses, then every other week thereafter. Bleomycin, 10 units/m² IV bolus, was followed by 10 units/m²/day infusion for 4 days (3-7 and 31-35). Vinblastine was given at 5 mg/m² every other week. Doses of vindesine, vinblastine, and bleomycin were not escalated. The maximum tolerated dose (MTD) of the carboplatin, vindesine bleomycin regimens was reached at a carboplatin dose of 250 mg/m² and the MTD was influenced by the weekly vindesine in the initial 4 weeks of therapy. The MTD of the carboplatin and vinblastine regimen was reached at a carboplatin dose of 500 mg/m². Dose-limiting toxicity of all three regimens was leukopenia. Although nonhematological toxicity of the carboplatin and vinblastine regimen included peripheral neuropathy and emesis, therapy was easily administered in an outpatient setting. The recommended Phase II dose of carboplatin is 450 mg/m² in combination with vinblasrine at this dose and schedule for previously untreated patients. Twelve patients demonstrated major responses with the various regimens including 5 of 24 patients with adenocarcinoma of the upper gastrointestinal tract.     

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PURPOSE: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. PATIENTS AND METHODS: Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. RESULTS: Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.     

Carboplatin and hypofractionated accelerated radiotherapy: a dose escalation study of an outpatient chemoradiation schedule for squamous cell carcinoma of the head and neck

AimTo examine the feasibility and determine the maximum tolerated dose of outpatient carboplatin given with synchronous hypofractionated accelerated radiotherapy for squamous cell carcinoma of the head and neck (SCCHN).Materials and methodsPatients with stages II–IV SCCHN and unresected primary tumour were treated with synchronous carboplatin given in an outpatient setting on day 1 and day 21 in cohorts of three to six patients with incremental area under curve (AUC) factors commencing at 3.5. Grade 3 mucositis persisting for 4 weeks in two patients in a cohort was considered dose limiting.ResultsA total of 19 patients were enrolled and assessable for toxicity. All 19 patients completed 55 Gy of radiotherapy and were assessable for response. Grade 3 mucositis lasting 4 weeks or more was seen in three patients, two of them received AUC 5 carboplatin. A complete response was seen in 16 patients, with a further patient having a partial response, giving a response rate of 89%. With a median follow-up of 24 months (range 11–30 months), 13 patients were alive with no evidence of recurrent disease. Local recurrence had occurred in four patients with distant spread in three patients.ConclusionCarboplatin with concurrent hypofractionated accelerated radiotherapy is feasible for patients with advanced SCCHN and good performance status. The recommended phase II dose of carboplatin given in week 1 and week 4 with 55 Gy in 20 fractions is AUC 4.5.     

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.     

局部晚期鼻咽癌同期放化疗顺铂单药每周方案剂量递增临床研究

Objective  

The purpose of this study was to define the maximum tolerated dose (MTD) by describing the doselimiting toxicity (DLT) of weekly cisplatin concurrently with conventional plus 3-dimensional conformal radiotherapy (CT + 3DCRT) in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC).     

替尼泊苷联合放疗治疗术后脑胶质瘤的I期临床试验

目的观察替尼泊苷（VM26）加放疗治疗术后脑胶质瘤的毒性、耐受剂量及临床可行性。方法20例脑胶质瘤（Ⅲ、Ⅳ级）术后患者为研究对象,照射野参考增强CT和MRI影像学检查所见,包括病灶外3cm,2Gy／次,总剂量Dr 60Gy,30分次,照射总时间6周。VM26分50、75、100mg／m^2 3个剂量级,每剂量组至少5例,如无明显不良反应进入下一剂量组,直至找到最大耐受量（MTD）,1次／周,共4次。结果主要不良反应为骨髓抑制。第2个剂量级中有4例出现Ⅲ、Ⅳ度骨髓抑制,MTD为75mg／m^2。结论术后脑胶质瘤照射加VM26综合治疗具有临床可行性,最大耐受剂量75mg／m^2,推荐Ⅱ期临床剂量为50mg／m^2。     

Phase I/II study of daily carboplatin, 5-fluorouracil and concurrent radiation therapy for locally advanced non-small-cell lung cancer

A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities and the response rate of carboplatin and 5-fluorouracil administered daily with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, unresectable stage IIIA or IIIB non-small-cell lung cancer (NSCLC) were enrolled. Carboplatin (20-40 mg m(-2) 2-h infusion, daily) and 5-fluorouracil (200 mg m(-2) 24-h continuous infusion, daily) were administered concurrently with radiotherapy on days 1-33. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions on days 1-40. In the phase I portion, the daily dose of carboplatin was escalated from 20 to 40 mg m(-2). Once the maximum tolerated dose (MTD) and recommended dose (RD) of carboplatin was determined, the study entered the phase II portion. In the phase I portion, the daily MTD and RD of carboplatin were 40 and 35 mg m(-2), respectively. The dose-limiting toxicity was neutropenia. In the following phase II study, 30 patients were entered and the objective response rate was 76.7% (95% CI, 62-92%) and the local control rate was 85.7%. The median survival time was 19.8 months, with a survival rate of 70% at 1 year, 36.7% at 2 years. The major toxicities of treatment were neutropenia (>or=grade 3, 87.9%) and thrombocytopenia (>or=grade 3, 23.3%). This combined therapy for locally advanced non-small-cell lung cancer is promising and shows acceptable toxicity.     

三维适形放疗联合诱导化疗和紫杉醇同期化疗不能手术Ⅲ期非小细胞肺癌的疗效分析

目的 观察诱导化疗和三维适形放疗(3DCRT)联合每周紫杉醇治疗非小细胞肺癌(NSCLC)的疗效及毒性.方法 56例不能手术的Ⅲ期NSCLC患者予紫杉醇(175 mg/m2第1天)加卡铂(AUC=5～6第1天)诱导化疗2～4个疗程,化疗后3～4周内开始3DCRT,剂量在满足V20≤31%,脊髓≤50 Gy的条件下给予尽可能高(平均60.75 Gy),联合每周紫杉醇40 mg/m2同期化疗.结果 同期放化疗期间,3例因3+4级放射性肺炎,1例因3级心脏毒性终止治疗,2例因身体虚弱分别中断治疗7、12 d,其余均按计划完成治疗.白细胞下降发生率为58.9%(1例为3级,余为1、2级),3级淋巴细胞下降发生率达75.O%.主要急性毒性为放射性食管炎和放射性肺炎,≥2级发生率分别为38%和25%.放射性食管炎3级3例,放射性肺炎3级2例,4级1例.2、3、4级晚期食管损伤各1例,肺纤维化2级9例.肺原发灶总有效率为69.7%.1年生存率分别为72.3%,1年局部无进展生存率为62.7%.局部复发率为32.1%,远处转移率为39.3%,远处转移与局部复发仍是死亡的主要原因.结论 诱导化疗后3DCRT结合每周紫杉醇治疗局部晚期NSCLC耐受性较好,近期疗效好,远期疗效有待继续观察.     

Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR).

BACKGROUND: Single-agent platinum and single-agent pegylated liposomal doxorubicin (PLD) are both effective in the treatment of gynecologic malignancies. Based on evidence that combination platinum-containing regimens offer superior efficacy versus single-agent regimens, we conducted this study to determine the maximum tolerated dose (MTD) of PLD in combination with carboplatin. PATIENTS AND METHODS: In this phase I/II dose-finding study, six courses of PLD (20, 30, 40 or 50 mg/m2) and carboplatin (AUC 6) were administered every 28 days to women with advanced gynecologic malignancies. Three to six patients were treated at each dose level; an additional 12 patients were treated at the MTD. RESULTS: PLD 40 mg/m2 was identified as the MTD when administered with carboplatin. Five of 18 patients experienced a dose-limiting toxicity at the MTD; two patients had grade 3/4 neutropenia, and one each had grade 3 emesis and grade 3 thrombocytopenia and thrombosis. No patient developed cardiotoxicity. In 11 patients evaluable for response, there were two complete responses, two partial responses and four patients with stable disease. CONCLUSIONS: The MTD for PLD when administered in combination with carboplatin is 40 mg/m2. This regimen is well tolerated and offers promising activity in women with advanced gynecologic malignancies.     

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. PATIENTS AND METHODS: The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). RESULTS: Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. CONCLUSION: Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.     

A phase I/II trial of induction chemotherapy with carboplatin and gemcitabine followed by concurrent vinorelbine and paclitaxel with chest radiation in patients with stage III non-small cell lung cancer

PURPOSE: We designed a phase I/II trial in order to evaluate the efficacy and tolerability of induction carboplatin and gemcitabine and the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of subsequent chemoradiotherapy with weekly vinorelbine and paclitaxel in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients had pathologically confirmed N2-N3 stage NSCLC, adequate end-organ function, and ECOG performance status 0-2. Carboplatin was administered at an AUC of 5 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days, for two cycles, followed by weekly vinorelbine 10-15 mg/m2 and paclitaxel 50 mg/m2 and conventional chest radiotherapy up to 66 Gy. Patients with resectable disease underwent thoracotomy after 40-45 Gy. RESULTS: Thirty-nine eligible patients were enrolled; 17 had stage IIIB NSCLC. Grade 3 esophagitis developed in 4/5 patients on the second dose level of chemoradiotherapy (i.e. vinorelbine 15 mg/m2) and was considered dose-limiting. Of 34 patients treated at the maximum tolerated dose (i.e. vinorelbine 10 mg/m2), 2 patients (6%) had pneumonitis >grade 2 and 3 (9%), esophagitis >grade 2. Induction chemotherapy was well tolerated with only one patient developing >grade 2 non-hematologic toxicity (nausea). Forty-one percent of patients had an objective response after induction chemotherapy and 51% after chemoradiotherapy. Nineteen patients, 16 of whom had stage IIIA, underwent surgical resection. The pathologic complete response rate was 16% (42% in the mediastinal lymph nodes). With a median follow-up of 31 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 23 and 34%, respectively, and the median OS was 25 months. CONCLUSIONS: We identified a well-tolerated and active chemoradiotherapy regimen. Survival results are promising and the addition of a biologic agent to this regimen is of interest.     

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: preliminary results of a prospective phase II study.

PURPOSE: Hyperthermia has been used in several trials to treat pelvic cancers without excessive toxicity and with positive results. The aim of this study was to evaluate feasibility and results in terms of biochemical recurrence-free, disease-free survival, overall survival, and treatment toxicity profile of hyperthermia combined with radiotherapy in locally advanced high risk prostate cancer. PATIENTS AND METHODS: From November 1998 to December 2004, 144 patients with locally advanced prostate cancer (LAPC) were enrolled in a phase II study. They were treated using conformal radiotherapy (CRT) plus local hyperthermia (LHT) and androgen suppression therapy (AST). Treatment modalities consisted of: 1) CRT with a mean dose of 74 Gy (2 Gy/fraction/5 fractions per week); 2) LHT: one session per week during the first, second, third, and fourth week of the radiotherapy course; 3) AST was administered as neo-adjuvant and adjuvant therapy in more than 60% of patients. RESULTS: The median follow-up time was 51.7 months. Four patients were lost at follow-up. Of 140 evaluated patients, four died because of intercurrent diseases and 12 because of progression of disease. Patients were evaluated in terms of five-year overall survival (87%), and five-year biochemical progression-free survival (49%). No significant side effects, except symptoms related to AST have been reported. No late grade 3 toxicity occurred. CONCLUSIONS: In advanced high risk prostatic cancer, hyperthermia is feasible and well tolerated. It may be useful to enhance the radiotherapy efficacy at intermediate dose in order to avoid higher doses of irradiation which increases acute and late sequelae. The advantage of LHT combined with CRT should be confirmed by a randomized phase III trial, comparing irradiation plus AST with or without hyperthermia.     

非小细胞肺癌三维适形放疗剂量递增的临床研究

目的通过临床剂量递增获得非小细胞肺癌（NSCLC）三维适形放射治疗的最大耐受剂量并观察其疗效。方法对84例Ⅰ～Ⅲ期NSCLC采用三维适形放射治疗（3D-CRT）,不进行区域淋巴结预防性照射。在CTV照射患者60Gy（2Gy/次,1次/天,5天/周）后,开始对GTV进行剂量递增。2～4Gy/次,递增次数为3～11次。根据肺V20和将患者分为V20〈25%组和V2025%～36%组,两组患者再根据总剂量分剂量亚组,观察放射性损伤发生率和疗效。以≥15%的患者出现3级以上急性放射性肺损伤（RTOG）为限制剂量递增标准。结果全组84例。V20〈25%组45例,剂量亚组分别为70Gy、74Gy、78Gy、82Gy。3级放射性肺炎发生率为4.4%（2/45）。V2025%～36%组39例,剂量亚组分别为66Gy、70Gy、74Gy、78Gy。3级放射性肺炎发生率为5.1%（2/39）。全组中位生存时间14个月,1、2年总生存率分别为69.5%、52.8%,1、2年局部控制率分别为79.7%、53.6%。随着剂量增加,1、2年生存率和局部控制率有所增高,但统计学检验均无统计学差异（P〉0.05）。结论采用3DCRT治疗NSCLC时,提高局部放射剂量应考虑正常肺组织所受照射的剂量和体积。当V20〈25%时,可以安全地递增到82Gy,其放射性损伤可以接受;当V20为25%～36%时,可以递增到76Gy。但当V20〉30%时,增加到更高的放射剂量应谨慎,而提高局部剂量对生存率和局部控制率的意义仍有待进一步研究。     

Phase I study of conformal radiotherapy with concurrent gemcitabine in locally advanced bladder cancer

PURPOSE: A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m(2) in increments of 50 mg/m(2) per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. RESULTS: All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m(2). Dose-limiting toxicity was observed at 150 mg/m(2) with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m(2) with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. CONCLUSION: The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m(2), with a maximal recommended dose of 100 mg/m(2). This dose regimen has now entered Phase II clinical trials.     

小细胞肺癌的三维适形放射治疗

目的 分析三维适形放射治疗（3DCRT）在小细胞肺癌（SCLC）治疗中的可行性、效果和放射损伤情况。方法 19例SCLC患者中,局限期18例,广泛期1例。18例采用放化疗综合治疗,1例采用单独放疗。放疗单次剂量2Gy,每周5次,中位总剂量54Gy。化疗多采用卡铂或顺铂＋VP-16为主的方案,4～6个周期。中位随访24个月。结果 （1）全组患者CR率为31．6％（6／19）,PR率为47．4％（9／19）,SD率为21．1％（4／19）,有效率为79．0％。1年总生存率（OS）为71、7％,2年OS为35．8％,中位生存时间为19个月。1,2年无局部进展生存率均为94．7％。（2）2级急性放射性肺损伤为5．3％（1／19）,2级晚期放射性肺损伤为5．3％（1／19）,2级急性放射性食管损伤10．5％（2／19）,2级血液学毒性为10．5％（2／19）。结论 3DCRT用于SCLC治疗是可行的,患者能够获得较好的近期疗效和2年生存率,SCLC的三维适形放射治疗值得进一步研究。     

The impact of conventional or hypofractionated radiotherapy on voice quality and oncological outcome in patients with early glottic cancer

The hypothesis being tested in this study is that hypofractionated radiotherapy is well tolerated and not lower in terms of oncological outcome than conventional radiotherapy. Forty patients with histologically proven glottic cancer were included in the analysis. Twenty-two were treated by hypofractionated radiotherapy (3D-HFRT) (25 fractions of 2.4 Gy delivered daily to a total dose of 60 Gy). This group was retrospectively compared to 18 subjects who met the same inclusion criteria and who were treated with conventional radiotherapy (3D-CRT) (33 fractions of 2 Gy delivered daily to a total dose of 66 Gy). One year after RT treatment in 10 patients (5 in the arm-1 and 5 in the arm-2) mild dysphonia persisted. The other patients achieved a complete recovery of the overall quality of voice with no significant difference documented between the two groups. At 3 years the local control rate was 100% for the patients treated with hypofractionated radiotherapy and 96% for the patients treated with conventional regimen. The statistical analysis did not show any significant difference in local control between the two groups (p=0.45). No significant acute and late toxicity was documented in both groups. Subjects with early glottic cancer seem to experience comparable levels of morbidity irrespective whether they were treated by hypofractionated or conventional conformal therapy without any worsening of the tumor local control. Thus, we provide clinical evidence to justify trends already emerging toward hypofractionated regimens in early glottic cancer.