局限期小细胞肺癌化疗联合加速超分割放疗疗效初步分析

背景与目的:局限期小细胞肺癌(small cell lung cancer,SCLC)对放疗和化疗均敏感.放疗可提高局限期SCLC患者总生存率,降低局部复发率.本研究总结在化疗基础上应用加速超分割放射治疗(hypedractionated accelerated radiotherapy,HART)对局限期SCLC的疗效,评价相关治疗毒性,归纳治疗失败方式.方法:55例局限期SCLC患者经过EP方案诱导化疗,放疗后再以EP方案巩固化疗,完全缓解(complete remission,CR)者行预防性全脑照射(Prophylactic cranial irradiation,PCI).治疗结束后对患者进行随访,并评价其疗效及毒副作用.结果:55例患者放化疗结束时总有效率(CR PR)为87.3%.1、3、5年总生存率分别为79.1%、40.3%、16.1%,中位生存时间18.7个月.Ⅲ度和Ⅳ度血液学毒性分别为23例(41.8%)和16例(29.1%);Ⅰ度和Ⅱ度急性放射性肺炎分别为21例(38.2%)和2例(3.6%),Ⅰ度和Ⅱ度放射性食管炎分别为29例(52.7%)和12例(21.8%),未发生Ⅲ～Ⅳ度非血液学毒性.11例(20.0%)患者出现Ⅰ度肺纤维化,5例(9.1%)为Ⅱ度.2例(3.6%)发生Ⅰ度后期食管损伤.16例(29.1%)局部/区域复发.21例(38.2%)发生远处转移.结论:EP方案化疗合并HART治疗局限期SCIJC毒性轻至中度,患者可以耐受.局部复发和远处转移为主要治疗失败原因.     

Simultaneous chemoradiotherapy with irinotecan and cisplatin in limited disease small cell lung cancer: a phase I study

INTRODUCTION: Early radiotherapy concurrent with chemotherapy appears to have prognostic benefits in patients with limited disease SCLC. Irinotecan/cisplatin have been shown to be superior to a standard treatment with etoposide/cisplatin in extensive disease SCLC. The present phase I study aims to assess the feasibility of irinotecan/cisplatin administered concurrently with radiotherapy. PATIENTS AND METHODS: Twelve patients were treated concurrently with conventional fractionated radiotherapy (1.8-45 Gy + 9 Gy (RP)) and two cycles of irinotecan (40/50/60 mg/m2, Day 1/8/15, 29/36/43) and cisplatin (20 mg/m2, Days 1-3, 29-31), and four cycles of consolidation chemotherapy (CT). In addition, patients in complete remission (CR) received prophylactic cranial irradiation (PCI). Dose-limiting toxicity (DLT) was defined as any case grade III/IV non-hematological toxicity (esophagitis grade IV), grade IV leukopenia or grades III/IV thrombopenia (CTC) during RCT. RESULTS: No DLT was observed; an irinotecan dose of 60 mg/m2 is recommended. 3/12 patients developed grade III leukopenia, one grade II pneumonitis. The predominant toxicity was esophagitis, grade II in 7/12 patients, grade III in 5/12. After RCT 7/12 patients were in CR, systemic progression was not observed during RCT. CONCLUSION: Concurrent RCT with irinotecan (60 mg/m2) and cisplatin followed by four cycles of CT can be safely administered.     

Limited small-cell lung-carcinoma - high complete response rate and survival with short intensive chemotherapy and extensive irradiation - results of a pilot-study

Sixteen patients with limited small-cell lung carcinoma (SCLC) were treated with three monthly courses of intensive chemotherapy (cisplatin: 40 mg/m2/day (D), D1, D2 and D3; cyclophosphamide: 750 mg/m2/D, D4 and D5; adriamycin: 50 mg/m2/D, D5; vindesine: 2 mg/m2/D, D1 and D5; etoposide: 100 mg/m2/D, D1, D2 and D3; methylprednisolone: 120 mg/m2/D, D1 to D5). Thoracic and prophylactic brain plus spinal area irradiations were performed after completion of the third chemotherapy cycle. The complete response rate was 100%. Of these 16 patients, 7 experienced a relapse from 5 to 31 months after completion of treatment. The three-year survival rate was 54%. The main toxicities were hematological (neutropenia and thrombocytopenia) and digestive. We conclude from this pilot study that intensive five-drug chemotherapy is a highly effective regimen for limited SCLC. This intensive chemotherapy regimen and extensive irradiation is feasible without major toxicity. This type of intensive combined-modality program deserves further study to definitely establish its long-term efficacy in localized SCLC.     

Tolerance of radiotherapy and chemotherapy in elderly patients with bladder cancer

Bladder-sparing radiotherapy with concurrent chemotherapy may be a reasonable alternative to cystectomy in patients with invasive bladder cancer. The purpose of this study was to determine the tolerance of combined treatment in elderly patients. In this retrospective study, the records of patients 70 or more years of age with stage T2-T4a, N0, M0 disease who were treated with bladder-sparing regimens between 1985 and 2000 were examined for toxicity. Of 149 consecutive patients treated for cancer of the bladder, 14 patients met eligibility criteria. The median age was 79 years. At a median follow-up of 17 months, the median survival was 19 months. All patients had at least mild toxicity, with 6 of 14 patients having grade III to IV toxicity. Grade III to IV toxicities included one patient with grade IV neutropenia, three with grade III gastrointestinal toxicities, one patient with grade III urinary frequency, one patient with grade IV ureteral obstruction who required stent placement, and one episode of hydration-induced grade III heart failure. Two of 14 patients stopped chemotherapy and 5 patients required dose reductions for toxicity. The observed rates of toxicity compare favorably with studies of bladder-sparing therapy in patients with median ages less than 70 years. Our study shows that bladder-sparing radiotherapy with concurrent chemotherapy is feasible in patients 70 or more years of age, and should be considered for such patients if they are inoperable or strongly wish to avoid cystectomy.     

High-dose methotrexate for elderly patients with primary CNS lymphoma

The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL.     

High-dose 3-dimensional conformal radiotherapy with concomitant vinorelbine plus carboplatin in patients with non-small cell lung cancer: A feasibility study

The aim of this study was to evaluate the feasibility of high-dose 3-dimensional conformal radiotherapy (3DCRT) (70 Gy) with concomitant vinorelbine (NVB) plus carboplatin (CBP) chemotherapy in patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with 3-dimensional conformal radiotherapy in conventional fractionation: 2 Gy/fraction, 1 fraction/day, 5 fractions/week; total dose 70 Gy. The radiotherapy planning of every case had met the following conditions: the percentage of total lung volume receiving 20 Gy (V20) ≤30% and the percentage of total lung volume receiving 30 Gy (V30) ≤20%. Chemotherapy was commenced on the first day of radiotherapy: NVB 25 mg/m(2), day 1 and day 8, CBP at AUC of 5 mg/ml(-1).min(-1), day 8, repeated for 28 days, two concomitant cycles during radiotherapy, and not more than 4 cycles following radiotherapy. A total of 37 patients were recruited and each of them completed the entire radiation procedure. No Grade V toxicity was observed within the group. The hematological toxicity rates were: Grade III/IV neutropenia was observed in 18.9% (7/37) of cases, Grade III/IV thrombocytopenia in 8.1% (3/37) of cases, but no cases of Grade III/IV anemia were noted. For non-hematological toxicities the rates were: Grade III radiation pneumonitis, 8.1% (3/37) of cases; Grade III radiation esophagitis, 13.5% (5/37); but no cases of Grade IV/V non-hematological toxicities. High-dose 3DCRT also achieved a favorable efficacy: the complete response (CR) rate was 13.5% (5/37) and the partial response (PR) rate was 64.9% (24/37). The total response (CR+PR) rate was 78.4% (29/37). The median survival time was 12 months and the 1-year overall survival rate was 45.1%. Given that 35% of patients in the study had stage IV disease, the survival results were comparable with other similar studies. In conclusion, in our small-sample exploratory study, the high-dose regimen of 70 Gy using 3DCRT with concomitant NVB plus CBP was feasible for patients with NSCLC. Further evaluation of this regimen is ongoing in a prospective controlled phase II trial.     

同步放化疗和单纯放疗治疗ⅡB～ⅢB期宫颈癌的疗效比较

背景与目的:同步放化疗已成为局部晚期宫颈癌的标准治疗模式,但对于放疗联合何种方案的化疗效果最佳,目前尚无一致意见.本研究中我们比较同步放化疗与单纯放疗,以及同步放化疗不同化疗方案的疗效及毒副反应.方法:2003年1月至2004年12月江西省妇幼保健院收治的符合人组标准的ⅡB～ⅢB期宫颈癌患者285例,按住院序号随机分为单纯放疗组142例,同步放化疗组143例.同步放化疗组又按化疗方案不同分为:BP(博来霉素 顺铂)方案同步放化疗51例,TP(紫杉醇 卡铂)方案同步放化疗47例,FP(氟尿嘧啶 顺铂)方案同步放化疗45例.比较单纯放疗组与同步放化疗组患者的3年生存率和不良反应,同时对同步放化疗三种不同化疗方案组的3年生存率及不良反应进行比较.结果:全组中位随访时间为42个月,单纯放疗组与同步放化疗组的3年生存率分别为65%和75%,两组比较差异有统计学意义(P=0.042).单纯放疗组Ⅲ～Ⅳ度急性毒副反应低于同步放化疗组(P<0.001),迟发性毒副反应两组差异无统计学意义(P=0.613).同步放化疗组BP方案、TP方案、FP方案的3年生存率分别为74%、80%和71%,三组间比较差异无统计学意义(P=0.792).三组Ⅲ～Ⅳ度急性及迟发性毒副反应发生率相似.结论:与单纯放疗相比,同步放化疗可明显提高ⅡB～ⅢB期宫颈癌患者的疗效.在同步放化疗三种不同的化疗方案中,紫杉醇联合卡铂方案组患者3年生存率略高于其他两种化疗方案,毒副反应可耐受,值得进一步研究.     

Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-na?ve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.     

Concurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation

OBJECTIVE: To assess the feasibility and outcome of concurrent chemoradiotherapy (CT-RT) with large regional field and high-dose external beam boost irradiation in thoracic esophageal cancer. METHODS: Patients with clinical stage T1 (submucosal)-4N0-1M0 (UICC 1997) squamous cell carcinoma of the thoracic esophagus were eligible. Radiotherapy consisted of regional irradiation (extending from supraclavicular fossa to the paracardial area) with 39.6 Gy followed by high-dose external beam boost up to 66.6 Gy (1.8 Gy/day, five times per week). Two-hour infusion of cisplatin (80 mg/m(2) on day 1) and continuous infusion of 5-fluorouracil (800 mg/m(2)/day on days 2-6) were administered concurrently with radiotherapy, every 3-4 weeks, for two cycles. RESULTS: Thirty patients (stage I, 3; stage II, 11; stage III, 16) were entered into the study. Twenty-one patients (70%) completed the planned treatment. In elderly (> or = 70 years) patients, four of six withdrew. Grade 3 and 4 toxicities (NCI-CTC) were observed in 20 (67%) and three (10%) patients, respectively. Major toxicities were blood, gastrointestinal (i.e. nausea and esophagitis) and pulmonary. There was no grade 5 (fatal) toxicity. The median follow-up period for surviving patients was 27 months (range: 9-49 months). The median survival time was 21 months. The 1- and 2-year survival rates were 65 and 49% for all 30 patients. The incidence of esophageal stricture (grade 1-2: RTOG) was 21%. No patient suffered fistula formation. CONCLUSIONS: Despite poor compliance for elderly patients and frequent severe toxicities, our concurrent CT-RT resulted in a favorable outcome in thoracic esophageal cancer.     

Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results

Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.     

Resultados a largo plazo de radioterapia y quimioterapia concomitante en cáncer microcítico de pulmón, enfermedad limitada al tórax, fuera de ensayos clínicos

Introduction

Chemotherapy combined with radiotherapy can improve local control and survival in patients with small cell lung cancer (SCLC).

Material and methods

We used cisplatin and etoposide (PE) with concurrent thoracic radiation therapy (TRT) followed by prophylactic cranial irradiation (PCI) in patients achieving a complete response. The objective was to evaluate the efficacy and toxicity of this regime in patients with localised SCLC. Patients (n=89) diagnosed with localised SCLC were treated with PE (4 to 6 cycles) together with TRT (50–60 Gy).

Results

The response rate was 92% (62%CR, 30%PR). The 20 patients with CR had PCI administered. Grade III–IV toxicities were 68% neutropenia, 23% thrombocytopenia, 23% anaemia and 24% severe dysphagia. Median overall survival rate was 17 months (probable survival rate of 35% at 2 years).

Conclusions

The treatment is feasible and provides acceptable survival rates despite the accompanying toxicity. It is recommended that PCI be provided for all patients achieving complete response.     

Late sequela after treatment of childhood low-grade gliomas: a retrospective analysis of 69 long-term survivors treated between 1983 and 2003

Summary Purpose The prognosis for patients with glioblastoma multiforme remains poor. Phase II studies, meta-analyses and a phase III study show that concurrent chemoradiotherapy has an advantage over irradiation alone. In this study the effectiveness of concurrent chemoradiotherapy with Topotecan and an adjuvant chemotherapy with Topotecan was investigated. Patients and method Forty-two patients with predominantly unfavourable prognosis factors were included in the study and treated as follows: hyperfractionated accelerated radiotherapy (2×1.75Gy to 45.5 + 12.25 Gy (RP)) with a concurrent, continuous infusion of Topotecan (0.5 mg/m²/d, days 1–21). On day 28 the adjuvant chemotherapy (three courses) was begun according to the same scheme. Result Haematological toxicities were 13/42 (30%) grade III leucopenia, 2/42 (4%) grade IV, as well as 5/42 (10%) grade III thrombopenias and 1/42 (2%) grade IV. 30/42 (71%) patients showed improvement or stabilisation of an existing neurological symptomatic complex. The median time to progression was 7.2 (+/− 0.8) months, the median total survival was 10 (+/− 1.2) months, the 2 year survival rate 4.7 (+/− 0.3)%. Prognostic factors were age, surgical radicality, performance status and the tumour volume before therapy. Summary Concurrent chemoradiotherapy and an adjuvant chemotherapy with Topotecan is feasible at acceptable toxicity levels also for patients with a moderate performance status. The patients benefit from the improvement of the clinical symptomatic complex and, even with unfavourable prognosis factors, have a higher median survival in comparison to data published on similar groups of patients given only radiotherapy.     

Treatment of advanced Hodgkin's disease: EBVD versus intensive brief chemotherapy

We start a controlled clinical trial to assess efficacy and toxicity of EBVD (epirubicin, bleomycin, vinblastine and dacarbazine) with an intensive and brief program of seven drugs administered weekly for 12 weeks in previously untreated patients with advanced Hodgkin's disease. Two hundred and sixty four patients were randomized to receive EBVD chemotherapy (134 cases) or intensive chemotherapy (130 cases). Eligible patients were either previously untreated stages III or IV. Patients with bulky disease received adjuvant radiotherapy. In an intent to treat analysis, all patients were evaluable for efficacy and toxicity. Complete response rate to the two regimens were similar (88 and 84%, respectively). However, actuarial 5 years overall survival rates were 87% (95% confidence interval (CI): 78-94%) for the EBVD regimen, which is statistically different to 59% (95% CI: 48-66%) for the intensive program (p < 0.01). Event-free survival were 83% (95% CI: 74-89%) for EBVD and 65% (95% CI: 58-71%) for the intensive program (p < 0.01). Significantly, more episodes of granulocytopenia grade III-IV, infection-related granulocytopenia, death-related infection even early hematological support with granulocyte colony stimulating factor were seen with the intensive, program. In the present single center trial, intensive chemotherapy did not appear to have better results when compared with standard chemotherapy in patients with advanced Hodgkin's disease.     

胸部放疗分割与局限期小细胞肺癌失败模式的相关性研究

目的：分析比较加速超分割与常规分割胸部放疗后局限期小细胞肺癌失败模式的差异。方法：回顾性调查我院2006年10月至2012年12月期间住院治疗的114例局限期小细胞肺癌患者病历资料,记录患者的治疗前临床特征、放疗分割方案、复发转移部位和放疗毒副反应。结果：局部／区域或远地转移作为首先失败模式和总体失败模式在常规分割组和超分割组的差异均无统计学意义（P ＞0．05）。超分割组中 II －III 级放射性肺炎和放射性食管炎的发生率均较常规分割组明显增高,其差异有显著统计学意义（P ＝0．006和 P ＝0．001）。结论：小细胞肺癌加速超分割胸部放疗未改变局部／区域复发和远地转移模式,但明显增加治疗毒性。加速超分割胸部放疗是否优于常规分割值得进一步研究。     

Effect of Low-Dose Chest Irradiation Before Chemotherapy on the Rate of Local Failure in Small-Cell Lung Cancer

Purpose: To evaluate the rate of tumor recurrence within the irradiated volume after initial low-dose irradiation of limited-stage small-cell lung cancer (SCLC), to assess the tolerance of a sequential combination of low-dose chest irradiation followed by chemotherapy, and to confirm the responsiveness of limited-stage SCLC to low-dose irradiation.Methods and Materials: In this pilot study, 26 patients with limited-stage SCLC were treated by first-line 20-Gy thoracic irradiation followed 3 weeks later by chemotherapy (cisplatin, doxorubicin, and etoposide for six cycles).Results: We present our final results with a median follow-up of surviving patients of 7 years. The response rate to this low-dose irradiation was 83%, with an overall response rate to radiochemotherapy of 96% and a median survival of 21 months. No unexpected early or late toxicity was observed. The rate of initial isolated local failure was 8%, which compares favorably with other published series using higher doses of radiochemotherapy.Conclusion: An initial chest irradiation of 20 Gy before chemotherapy could be sufficient to reduce the risk of local failure during the time of survival of patients with limited-stage SCLC. Potential advantages of this treatment may be the prevention of resistance mechanisms to radiotherapy induced by preliminary chemotherapy and a reduced radiation-induced toxicity.     

Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: an integrated analysis

The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m(2) per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score > or =2; SCLC; and exposure to both cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.     

局限期SCLC超分割或大分割放疗同步化疗预后比较

目的 比较超分割或大分割放疗同步化疗对局限期SCLC的生存影响。方法 超分割和大分割组分别入组患者92、96例。超分割组采用45 Gy分30次,2 次/d。大分割组采用55 Gy分22次,1 次/d。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 超分割和大分割组患者1、2、5年PFS率分别为82%、61%、59%和85%、69%、69%(P=0.27),OS率分别为85%、41%、27%和77%、34%、27%(P=0.37)。多因素分析显示化疗开始到放疗开始时间≤43 d是PFS的有利因素(P=0.005),化疗开始到放疗结束时间≤63 d、PCI是OS有利因素(P=0.044、0.000)。超分割组和大分割组2、3级急性放射性食管炎发生率分别为28%、9%和16%、2%(P=0.009)。结论 采用加速超分割或大分割方案联合同步化疗的PFS及OS均显著提高。控制化疗开始至放疗开始、结束时间≤43 d、≤63 d有利于提高PFS和OS。但2、3级急性放射性食管炎的发生率超分割组显著高于大分割组。     

Pilot study of daily ifosfamide 1 g/m2 until grade III granulocytopenia as second-line chemotherapy for anthracycline-pretreated advanced soft tissue sarcoma

BACKGROUND AND AIMS: Second-line chemotherapy regimens for advanced soft tissue sarcomas after treatment failure or tumor relapse following anthracyclines are still investigational. The aim of the present study was to assess the activity of ifosfamide with a new schedule for patients with advanced soft tissue sarcoma failing to achieve remission or relapsing following anthracycline-containing regimens; it was attempted to individualize dosages and prevent excessive toxicity. STUDY DESIGN: A second-line chemotherapy regimen of ifosfamide 1 g/m2 daily, with drug withdrawal until the next cycle upon appearance of grade III granulocytopenia, was administered to 21 patients with advanced soft tissue sarcoma. All patients failed to achieve remission or relapsed following a first-line high-dose anthracycline regimen (epirubicin 180 mg/m2 or zorubicin 600 mg/m2 per cycle). The cycles were repeated every four weeks. RESULTS: The median number of cycles applied was three (range, 1-15). The ifosfamide dosage reached was 4-13 g/m2 per cycle, median 5 g/m2. A complete response was achieved in 1/21 patient (5%), no partial responses were observed, 4/21 patients (20%) had stable disease, and 16/21 (75%) had progressive disease. No difference in response and stable disease rates was observed between responders and non-responders to first-line chemotherapy. No difference in the ifosfamide dose reached was noted between patients receiving second-line chemotherapy directly following first-line therapy and those with a time interval between first- and second-line chemotherapy. The granulocytopenia grade III nadir lasted for a median of one day (range, 1-3) and other toxicities including hematological toxicity were mild and infrequent. CONCLUSIONS: In view of the swift regeneration from grade III granulocytopenia, continuation of the study with granulocytopenia grade IV as a limiting factor for ifosfamide dose escalation seems feasible, with the prospect of better efficacy without excessive toxicity.     

Can long-term survival be improved in patients with small-cell lung cancer (SCLC) and good performance status? Medical Research Council Lung Cancer Working Party.

Results from a long-term follow-up suggest that in patients with limited small-cell lung cancer (SCLC) and normal performance status intensive alternating chemotherapy and radiotherapy improve long-term survival rates. In a non-randomised study, 22 patients with SCLC of limited extent and good performance status were prescribed six cycles of etoposide, doxorubicin, cisplatin and cyclophosphamide at 4 week intervals with doses of thoracic radiotherapy following the second, third and fourth cycles. Although only six patients received all their prescribed treatment, nine (41%) were alive at 1 year, seven (32%) at 2 years, six (27%) at 3 years, and four are still alive at, respectively, 42, 47, 50, and 61 months, all four being in the subgroup of eight patients with WHO performance status grade 0 at the start of treatment. In a comparison with similar patients receiving conventionally scheduled chemotherapy and radiotherapy in a concurrent trial, no difference in survival was seen in the patients with performance status grade 1 or 2, but a large difference in favour of the alternating schedule in those with grade 0 status was seen. We encourage other investigators to report the results achieved with intensive treatment in patients with WHO grade 0 performance status at the start of treatment.     

Etoposide plus cisplatin with concurrent radiotherapy in the treatment of small-cell lung cancer

Introduction

Since the decade of the 80's, the etoposide plus cisplatinum regimen has been the standard treatment in patients with localised small-cell lung cancer (SCLC). Randomised trials have demonstrated the benefit of chemotherapy in combination with hyper-fractionated radiotherapy in this subset of patients.

Material and methods

Between January 1993 and June 1999, a total of 59 patients with localised SCLC were recruited into the study. All patients received 4 cycles of chemotherapy every 21 days. The first cycle was administered concurrently with hyper-fractionated radiotherapy. Prophylactic cranial irradiation (PCI) was administered subsequently when complete response was obtained.

Results

The proposed treatment schedule was successfully accomplished in 54 patients. The more important toxicities noted were oesophagitis and myelotoxicity, febrile neutropenia in 6 patients (10%), and oesophagitis grade IV in 9 patients (15%). Complete response was achieved in 39 cases (72%) and partial response in 11 (20%). Median survival was 20 months.

Conclusions

We conclude that the schedule combining etoposide + cisplatin with concurrent hyperfractionated radiotherapy is the best therapeutic scheme currently on offer in the management of patients with localised SCLC.