A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer: a preliminary report from the Okayama Lung Cancer Study Group

A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status < or = 2, age < or = 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m(-2), days 1-5) and 5-fluorouracil (5-FU) (500 mg m(-2), days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily, with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for N0-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (> or = Grade 3, 58% and 60% respectively). Other toxicities of > or = Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.     

Phase II study of bi-weekly docetaxel and carboplatin with concurrent thoracic radiation therapy followed by consolidation chemotherapy with docetaxel plus carboplatin for stage III unresectable non-small cell lung cancer

OBJECTIVE: Docetaxel and carboplatin (DC) have demonstrated activity as radiation sensitizers in pre-clinical studies. The aim of this phase II study was to evaluate the efficacy and toxicity of DC with concurrent thoracic radiation therapy (TRT) followed by consolidation chemotherapy with DC for stage III unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-three previously untreated patients with inoperable, locally advanced (LA) NSCLC received docetaxel 30 mg/m2 over 1 h and carboplatin at an AUC of 3 every 2 weeks for six courses--four courses during concurrent chemoradiotherapy and two courses following completion of radiotherapy. Concurrent TRT was performed in 2-Gy daily fractions to a total dose of 60 Gy. RESULTS: Among 32 evaluable patients, the overall response rate was 91%, with two complete responses (CR) and 27 partial responses (PR). Median survival time by intention-to-treat analysis was 27 months, with survival rates of 76% at 1 year and 61% at 2 years. Serious side effects were generally limited to grade 3 neutropenia in 6%, grades 3 and 4 pulmonary toxicity in 6 and 3%, respectively, and grade 3 esophagitis in 3% of patients. CONCLUSIONS: DC with concurrent TRT followed by consolidation chemotherapy was highly active with manageable toxicity in patients with stage III unresectable NSCLC.     

不可手术局部晚期NSCLC隔周恩度联合同步放化疗多中心五年生存分析

目的:评价隔周使用重组人血管内皮抑制素(恩度)联合以铂类为基础同步放化疗治疗不可手术局部晚期非小细胞肺癌(NSCLC)患者的5年生存情况。方法:2009—2015年间来自两项前瞻性研究的115例患者[2009—2012年临床试验(ClinicalTrials.gov,编号NCT01218594)和2012—2015年的...     

不能手术局部晚期非小细胞肺癌同步或序贯放化疗85例临床分析

目的：评价不能手术局部晚期非小细胞肺癌（ NSCLC）患者同步或序贯放化疗的疗效和不良反应。方法：2011年7月至2013年12月间初治接受同步或序贯放化疗的85例患者入组本研究,其中45例同步放化疗患者列入A组,40例序贯放化疗患者列入B组。A组采用放疗同步紫杉醇、顺铂化疗,B组采用单纯放疗,放疗结束后行紫杉醇、顺铂化疗。两组放疗方法相同,均为三维适型放疗,剂量60Gy/30f。对比两组治疗的疗效、不良反应和1、2年生存率。结果：85例患者均可评价疗效,随访率100%。A组与B组有效率分别为73.3%和50.0%（P﹤0.05）;1年局部控制率分别为51.1%和30.0%（P﹤0.05）;1年生存率分别为62.2%和42.5%（P﹥0.05）;2年生存率分别为37.8%和17.5%（P﹤0.05）。A组≥Ⅲ级放射性肺炎、放射性食管炎及Ⅲ~Ⅳ级骨髓抑制的发生率分别为6.7%、11.1%和28.9%,B组分别为5.0%、10.0%和27.5%。两组不良反应相似,均可耐受。结论：局部晚期NSCLC同步放化疗的疗效优于序贯放化疗,不良反应可耐受,同步放化疗是不能手术的局部晚期NSCLC标准治疗方法。     

局部晚期非小细胞肺癌VMAT初步疗效和不良反应分析

目的 评估VMAT用于局部晚期非小细胞肺癌(NSCLC)放疗近期疗效和不良反应。 方法 2016年间无法手术的局部晚期NSCLC患者共 58例接受同步放化疗或序贯放化疗,其中男 47例。放疗剂量为 38~66 Gy,53例(92%)患者放疗剂量≥56 Gy。放疗中位次数30次,单次剂量 1.8~3.0 Gy。28例(48%)患者接受同步化疗。 结果 中位随访时间9个月,1年总生存率84%,1年无进展生存48%。11例(19%)患者发生症状性放射性肺炎,其中1例患者因为放射性肺炎死亡。31例(53%)患者在放疗后半年内CT发现无症状性肺局部纤维化。17例(29%)患者出现2级食管炎,10例(17%)患者发生≥3级不良反应,其中9例为白细胞减少。 结论 采用VMAT行局部晚期NSCLC胸部放疗近期疗效理想,不良反应可接受,肺炎风险未见增加。     

Induction chemotherapy followed by concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer

The favourable experience with the combination regimen of vinorelbine, ifosfamide and cisplatin (NIP) in patients with metastatic non-small cell lung cancer (NSCLC) has led to a protocol assessing this regimen as an induction treatment in patients with stage III unresectable NSCLC, followed by thoracic radiotherapy with concurrent daily cisplatin as a radiosensitizer. Two cycles of NIP were administered 21 days apart; each cycle comprised i.v. vinorelbine 25 mg/m2 on days 1 and 8, i.v. ifosfamide 3 g/m2 on day 1 with MESNA as uroprotection, and i.v. cisplatin 50 mg/m2 on day 1. Radical thoracic radiotherapy commenced on day 43 to a total dose of 64 Gy and i.v. cisplatin 6 mg/m2 was given concurrently prior to each fraction of radiation as a sensitiser. Two more cycles of NIP were given to patients who responded favourably to the induction treatment about 2 weeks after completion of radiation. Between July 1995 and July 1997, 44 patients were treated with this protocol. This treatment schedule was generally well tolerated. Grade 3-4 neutropenia occurred in 50% of the patients and neutropenic sepsis was seen in 8. Grade 3-4 oesophagitis was uncommon. Most of the patients were able to complete the induction and concurrent chemoradiotherapy phase. Major response occurred in 75% of the patients with 2 (4.5%) complete responses (CR). A total of 6 patients achieved CR after chemoradiotherapy. At a median follow-up of 35 months, the median overall survival for all patients was 15 months with a 3-year survival rate of 24%. The median overall survival for stage IIIA patients was 19 months with a 3-year survival rate of 39% in contrast to 13 months' median overall survival and only 15% 3-year survival rate for stage IIIB. The NIP regimen results in a high response rate in NSCLC and this treatment programme seems to benefit selected patients with stage III disease.     

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer.

Both induction chemotherapy and concurrent low-dose cisplatin have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study was designed to investigate activity and feasibility of a novel chemoradiation regimen consisting of induction chemotherapy followed by standard radiotherapy and concurrent daily low-dose cisplatin. Previously untreated patients with histologically/cytologically proven unresectable stage IIIA/B NSCLC were eligible. Induction chemotherapy consisted of vinblastine 5 mg m(-2) intravenously (i.v.) on days 1, 8, 15, 22 and 29, and cisplatin 100 mg m(-2) i.v. on days 1 and 22 followed by continuous radiotherapy (60 Gy in 30 fractions) given concurrently with daily cisplatin at a dose of 5 mg m(-2) i.v. Thirty-two patients were enrolled. Major toxicity during induction chemotherapy was haematological: grade III-IV leukopenia was observed in 31% and grade II anaemia in 16% of the patients. The most common severe toxicity during concurrent chemoradiation consisted of grade III leukopenia (21% of the patients); grade III oesophagitis occurred in only two patients and pulmonary toxicity in one patient who died of this complication. Eighteen of 32 patients (56%, 95% CI 38-73%) had a major response (11 partial response, seven complete response). With a median follow-up of 38.4 months, the median survival was 12.5 months and the actuarial survival rates at 1, 2 and 3 years were 52%, 26% and 19% respectively. The median event-free survival was 8.3 months with a probability of 40%, 23% and 20% at 1, 2 and 3 years respectively. Induction chemotherapy followed by concurrent daily low-dose cisplatin and thoracic irradiation, in patients with locally advanced NSCLC, is active and feasible with minimal non-haematological toxicity. Long-term survival results are promising and appear to be similar to those of more toxic chemoradiation regimens, warranting further testing of this novel chemoradiation strategy.     

Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in stage III non-small cell lung cancer patients

ABSTRACT: PurposeThe aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III non-small cell lung cancer (NSCLC).Methods and materialsEighty-six patients with advanced stage NSCLC, treated with either IMRT only (66 Gy) or combined with (sequential or concurrent) chemotherapy were retrospectively included in this study. Overall survival and metastasis-free survival were assessed as well as acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity Scoring Criteria. RESULTS: Irrespective of the treatment modality, the overall survival rate for patients receiving 66 Gy was 71% (+/-11%; 95% CI) after one year and 56% (+/-14%) after two years resulting in a median overall survival of 29.7 months. Metastasis-free survival was 73% (+/-11%) after both one and two years. There were no statistically significant differences between the treatment groups. Treatment related esophageal toxicity was significantly more pronounced in the concurrent chemoradiotherapy group (p = 0.013) with no differences in pulmonary toxicity. CONCLUSIONS: This retrospective cohort study in advanced non-small cell lung cancer patients shows that IMRT is an effective technique with acceptable acute toxicity, also when (sequentially or concomitantly) combined with chemotherapy.     

62例不可手术的局部晚期非小细胞肺癌同步放化疗分析

目的：评价局部晚期不可手术的非小细胞肺癌同步放化疗的疗效和安全性。方法：对62例经细胞学或病理学明确诊断的局部晚期非小细胞肺癌患者进行同步放化疗,4个周期的NP加上同步放疗,第1周期NP化疗第1天就开始实施放疗。放疗采用15MV-X线,3D-CRT常规分割照射,总剂量60Gy。结果：可评价的60例患者,完全缓解11例,部分缓解36例,稳定11例,进展2例,总有效率为78.3%,1年、2年、3年生存率分别为90%,48.3%和23.3%,中位生存时间为23.2个月。结论：疗前正确评估合适的局部晚期非小细胞肺癌患者,同步放化疗有较好的1年、2年、3年生存率及中位生存时间,毒副反应多能耐受。     

UFT plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer--its application to outpatient practice

BACKGROUND: Combination chemotherapy with UFT and cisplatin is active and less toxic for advanced non-small cell lung cancer. This treatment is likely to be applied to concurrent chemoradiotherapy for locally advanced non-small cell lung cancer, especially in the outpatient setting. PATIENTS AND METHODS: Ten patients with unresectable stage III non-small cell lung cancer received the UFT plus cisplatin treatment combined with concurrent radiotherapy. The chemotherapeutic regimen consisted of oral administration of UFT 400 mg/m2 daily and venous infusion of cisplatin 20-25 mg/m2 on days 8-10. The administration of cisplatin was repeated every 3-4 weeks. Thoracic radiation started on day 8, and was completed to a total dose of 60-70 Gy. RESULTS: Adverse events (grade 3 or 4) occurred in 2 patients (esophagitis 2, leukopenia/neutropenia 1) with no treatment-related death. There were 7 partial responses (response rate 70.0%; 95% C.I., 41.6-98.4%). The median survival time was 18.7 months with a 1-year survival rate of 77.8%. Two patients uneventfully received the treatment in an outpatient setting. CONCLUSION: With regard to the quality of life of patients, UFT plus cisplatin with concurrent radiotherapy might be the treatment of choice for unresectable stage III non-small cell lung cancer.     

Uracil/tegafur plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination treatment using concurrent radiotherapy with cisplatin plus UFT, which is comprised of uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this Phase II trial, patients with unresectable stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was administered i.v. on days 8 and 36. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions from day 1. RESULTS: Seventy patients were enrolled and eligible, as follows: 57 males/13 females; mean age 61 ranging from 36 to 74; performance status 0/1:45/25; stage IIIA/IIIB, 14/56. A complete response was observed in two patients and a partial response in 54 patients, and the overall response rate was 81% (95% confidence interval; 70-89%). The median survival, the 1- and 2-year survival rates were 16.5 months, 67% and 33%, respectively. Grade 3/4 leukopenia occurred in 14%/1% of the patients. Grades 3 non-hematological toxicities were only reported in three patients with nausea, two with esophagitis and one with pneumonitis whereas no grade 4 non-hematological toxicity was observed. CONCLUSIONS: UFT plus cisplatin with concurrent radiotherapy is considered to be a feasible and effective treatment for locally advanced NSCLC patients. Additional study of this concurrent chemoradiotherapy is warranted.     

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.     

Induction chemotherapy with carboplatin/paclitaxel followed by surgery or standard radiotherapy and concurrent daily low-dose cisplatin for locally advanced non-small cell lung cancer (NSCLC)

Five-year survival in patients with unresectable non-small-cell lung cancer (NSCLC) is less than 10%. In the present phase II study, 43 patients with locally advanced stage IIIA or selected IIIB NSCLC were given four courses of carboplatin AUC = 6 and paclitaxel 200 mg/m2 (3-hour infusion), every 3 weeks. Responsive patients, when possible, underwent surgery followed by standard radiotherapy (50 Gy) or radiotherapy (60 Gy), with concurrent cisplatin as intravenous continuous infusion of 4 mg/m2/d. Sixteen of the 42 evaluable patients achieved partial response (38%) and 3 complete response (CR) (7%) for an overall response rate of 45% (95% CI 30.1-60.2). R0 resectability rate was 29%, with 21% of pathologic CRs. Three more CRs were achieved with concurrent chemoradiotherapy in responsive but unresected patients. Grade III/IV hematologic toxicity was 9%, while one perioperative death occurred. The median duration of response was 14 months (range: 3-44+); median survival was 15 months (range: 9-47+). One-year and 2-year survival rates were 51% and 22%, respectively. The median survival in the responsive resected patients was 26 months, with 2-year survival of 57%. Carboplatin/paclitaxel represents an effective and well-tolerated induction therapy, suggesting its possible role in combination with radiotherapy as neoadjuvant treatment in locally advanced NSCLC in alternative to cisplatin-based regimens.     

Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally advanced stage III non-small-cell lung cancer

Purpose  Our objective was to assess the efficacy and toxicity of concurrent chemoradiotherapy with cisplatin + weekly divided-dose docetaxel in patients with stage III non-small-cell lung cancer (NSCLC). Methods  A total of 34 patients aged less than 75 years old with locally advanced stage III NSCLC were enrolled. The patients received intravenous infusions of cisplatin (80 mg/m²; day 1) and docetaxel (20 mg/m²; days 1, 8, 15), followed by a week’s drug-free interval. Standard concurrent thoracic radiotherapy was given for 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results  Over Grade 3 neutropenia, esophagitis and pulmonary toxicities were observed in 23.5, 17.6 and 11.8% of the cases, respectively. One complete response and 20 partial responses were obtained, with an objective response rate of 61.8%. The median survival time was 26.4 months (95% CI 16.9—not reached) and the 1- and 3-year survival rates were 76.5 and 41.2%, respectively. Conclusion  Cisplatin + weekly docetaxel with concurrent radiotherapy is a feasible and effective regimen for locally advanced NSCLC.     

A Phase II Study of Gefitinib With Concurrent Thoracic Radiotherapy in Patients With Unresectable,Stage III Non–small-cell Lung Cancer Harboring EGFR Mutations (WJOG6911L)

Locally advanced non–small-cell lung cancer (NSCLC) is curable. Standard treatment is concurrent chemoradiotherapy, but its efficacy with cytotoxic agents seems to reach a plateau. Among patients with advanced NSCLC who have epidermal growth factor receptor (EGFR) mutation, EGFR-tyrosine kinase inhibitor is the key drug. Thus, a similar strategy should be tested in patients with locally advanced NSCLC who have EGFR mutation. This single arm, phase II study aims to explore the efficacy and tolerability of gefitinib with concurrent thoracic radiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. The primary endpoint is progression-free survival rate at 2 years. The secondary endpoints are overall response rate, progression-free survival, overall survival, and safety. A total of 27 patients will be enrolled in this trial.     

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.     

Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer: a feasibility study

Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.     

Concurrent chemoradiotherapy with low-dose cisplatin plus 5-fluorouracil for the treatment of patients with unresectable head and neck cancer

OBJECTIVE: The purpose of this study was to determine the efficacy of concurrent chemoradiotherapy using conventional radiotherapy combined with low-dose daily 5-fluorouracil (5FU) and cisplatin (CDDP) for the locally unresectable head and neck cancer patients. PATIENTS AND METHODS: From September 1996 through December 2000, we carried out a phase II study of concurrent chemoradiotherapy with low-dose CDDP plus 5FU for the treatment of patients with unresectable squamous cell carcinoma of the head and neck. Chemoradiotherapy consisted of irradiation with 1.6-2.0 Gy/day for 5 days per week up to a total dose 68 Gy and CDDP 3 mg/m2 by intravenous infusion over 1 h plus 5FU 150 mg/m2 by intravenous infusion over 24 h per day for 5 days per week. RESULTS: Ninety percent of the patients had stage IV disease, including 65% of patients with T4 disease. Thirty-three patients (83%) received the full treatment as planned; 39 (98%) received full-dose radiotherapy and 33 (83%) full-dose chemotherapy. Of the 40 patients evaluable for response, 20 (50%) achieved complete response (CR) and 12 (30%) partial response with an overall response rate of 80%. Among the 20 CR patients, 15 underwent endoscopic blind biopsies and 4 had positive lesions. The most frequently observed toxicity was mucositis. Ten patients developed grade III mucositis, and 3 patients required enteral nutritional support through a feeding tube. Grade III leukopenia, anemia and thrombocytopenia were observed in 28, 25 and 20% of the patients, respectively. The median duration of follow-up at the time of analysis was 18 months. The median survival time was 23 months. The responders survived longer (34 months) than the nonresponders (4 months; p < 0.05). CONCLUSION: This regimen is safe and efficacious in the treatment of patients with advanced unresectable head and neck cancer.     

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.     

Radiation Dose-escalated Chemoradiotherapy Using Simultaneous Integrated Boost Intensity-Modulated Radiotherapy for Locally Advanced Unresectable Thoracic Oesophageal Squamous Cell Carcinoma: A Single-institution Phase I Study

AimsAbout 80% of cases of locally advanced unresectable thoracic oesophageal squamous cell carcinoma recur within the irradiation fields after chemoradiotherapy. Radiation dose escalation using advanced radiotherapy techniques is expected to improve clinical outcomes by reducing local and regional recurrence. The current study aimed to determine the recommended escalated radiation dose for these patients.Materials and methodsPatients with locally advanced unresectable thoracic oesophageal squamous cell carcinoma with good performance status underwent chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with elective nodal irradiation. SIB-IMRT was delivered in five fractions per week. The radiation dose to the unresectable gross tumour was escalated from 66 Gy to a planned maximum dose of 72 Gy in 3 Gy increments in a standard 3 + 3 design. The doses to the resectable component, superficial tumours and elective nodal regions were fixed as 60, 51 and 48 Gy, respectively. Cisplatin and 5-fluorouracil were concurrently administered. Dose-limiting toxicity (DLT) was defined as acute grade 3 oesophagitis, grade 2 pneumonitis, grade 2 cardiac toxicity and a failure to complete planned radiotherapy within 60 days. Locoregional control and overall survival were estimated using the Kaplan–Meier method. Nine patients were enrolled.ResultsDLTs occurred in one of six and two of three patients at doses of 66 and 69 Gy, respectively. All DLTs were grade 3 oesophagitis. The recommended dose was determined as 66 Gy delivered in 30 fractions based on the predefined criteria. With a median follow-up period of 23 months, the 1-year locoregional control and overall survival rates were 67 (95% confidence interval = 19–90) and 78% (95% confidence interval = 36–94), respectively.ConclusionThe recommended radiation dose in chemoradiotherapy using SIB-IMRT with elective nodal irradiation was 66 Gy delivered in 30 fractions.