Treatment results of alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil--a phase II study

The present study was conducted to evaluate the therapeutic results of alternating chemoradiotherapy for locally advanced nasopharyngeal cancer. The subjects were 87 patients with stage II-IVB nasopharyngeal cancer. Alternating chemoradiotherapy was performed; initially, chemotherapy was administered, and then radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy were alternately performed. For chemotherapy, 5-FU at a dose of 800 mg/m2/24 h was intravenously administered for 5 days (days 1-5), and CDDP at a dose of 50 mg/m2/24h for 2 days was administered on day 6 and 7. The scheduled courses of alternating chemoradiotherapy were completed in 70 (80%) of 87 patients. Although 1 patient developed a transient neurological disturbance induced by hyper-ammonemia by metabolism of 5-FU, no severe adverse effects were noted in any other patients. In these 87 patients, the overall 5-year survival rate was 83% (95% confidence interval: 74-92%), and the progression free survival rate was 75% (95% CI: 66-85%). This method of alternating chemoradiotherapy yielded higher or at least similar survival rates and lower toxicities than concurrent chemoradiotherapy, and is worth trying in a randomized controlled study to compare with concurrent chemoradiotherapy.     

同步放化疗和新辅助化疗治疗ⅡB～ⅢB期子宫颈癌的疗效分析

目的探讨同步放化疗治疗ⅡB～ⅢB期子宫颈癌的疗效。方法将126例ⅡB～ⅢB期子宫颈癌患者随机分为同步放化疗组（治疗组）和化疗后放疗组（对照组）。对照组62例外照射加腔内治疗,当放疗剂量达到30Gy时用^192Ir腔内治疗,7．0Gy／次,1次／周。当外照射剂量达到46Gv时中间挡铅。A点剂量65～70Gy,B点剂量50—56Gy结束放疗,在放疗开始前给予顺铂（DDP）20mg静脉滴注,第1天至第5天,5-氟尿嘧啶（5-Fu）750mg静脉滴注,第1天至第5天,每28d重复。2个周期结束后开始放疗,放疗结束后继续原方案化疗2个周期,共4个周期。治疗组64例,放射治疗同对照组,在放疗开始时给予DDP20mg静脉滴注,第1天至第5天,5-Fu 750mg静脉滴注,第1天至第5天,每28d重复,共用4个周期。结果全部病例随访5年以上,随访率9414％。治疗组3、5年生存率分别为82．8％、65．6％;对照组3、5年生存率分别为67．7％、46．8％,两组差异有统计学意义（x^2=3．86,P〈0．05;x^2=5．01,P〈0．05）。两组生存曲线比较差异有统计学意义（x^2=4．26,P〈0．05）,不良反应差异无统计学意义。结论同步放化疗治疗晚期子宫颈癌疗效好,可以提高3、5年生存率。不良反应无明显增加。     

Dose escalation study of nedaplatin with 5-fluorouracil in combination with alternating radiotherapy in patients with head and neck cancer

BACKGROUND: This study, with a large number of patients, confirms that after administration of 5-fluorouracil (5FU), a higher dose of nedaplatin (NDP) can be safely administered rather than a single therapy of NDP, as demonstrated in a phase I study. METHODS: The subjects were 52 patients with stage II-IV (M0) head and neck cancer other than nasopharyngeal cancer. Alternating chemoradiotherapy was performed using the following method. Initially, chemotherapy was administered. For chemotherapy, 5FU at 700 mg/m2/24 h was intravenously administered for 5 days (days 1-5), and NDP was administered on day 6. We established three dose groups: level 1, 120 mg/m2; level 2, 140 mg/m2; and level 3, 150 mg/m2 (n = 13 or more per group). RESULTS: The maximum acceptable dose of NDP (150 mg/m2) was confirmed. The 5-year overall survival rates were 77% (95% CI: 66-90%) in all subjects and 75% (95% CI: 61-92%) in the stage III/IV patients. The 5-year progression-free survival rates were 73% (95% CI: 62-87%) in all subjects and 72% (95% CI: 57-89%) in the stage III/IV patients. CONCLUSIONS: After administration of 5FU, a higher dose of NDP can be safely administered. This alternating chemoradiotherapy showed potent antitumor effects. The efficacy of chemotherapy with NDP and 5FU should be compared to that of chemotherapy with CDDP and 5FU.     

Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): a feasibility study

BACKGROUND: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. PATIENTS AND METHODS: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m2). This was to be followed by 2 cycles of cisplatin/ vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. RESULTS: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. CONCLUSION: Oral vinorelbine 50 mg/m2 (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy.     

Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516)

BACKGROUND: In Japan, concurrent chemoradiotherapy is the standard treatment for unresectable esophageal cancer. The optimal combination of chemotherapeutic agents and radiotherapy dose remains controversial. The present study consists of a phase II trial of a cisplatin (CDDP)/5-fluorouracil (5-FU) infusion with concurrent radiotherapy in patients with unresectable, advanced esophageal cancer. METHODS: Between March 13, 1996, and April 28, 1998, 60 patients with advanced squamous cell carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis (M1 Lym) were enrolled in this study. CDDP 70 mg/m(2) was administered on days 1 and 29, and 5-FU 700 mg/m(2)/day was administered on days 1-4 and 29-32. Fractionated radiotherapy was performed on days 1-21 and 29-49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction. RESULTS: The overall response rate of all the 60 registered patients was 68.3% (41/60), and the complete response rate was 15% (9/60). The median survival time was 305.5 days, and the 2-year survival rate was 31.5%. One toxicity-related death occurred. The major form of toxicity exceeding grade 2 was found to be myelosuppression; grade 4 toxicity was observed in five patients. CONCLUSION: Based on the overall response rate, the results obtained from the present trial do not appear to be promising. However, it is currently suitable for the treatment of patients with unresectable, advanced esophageal cancer because of certain clinical advantages, a higher CR rate and a lower incidence of fistula formation. A phase II/III trial will be started in order to compare low-dose continual CDDP/5-FU infusion and concurrent radiotherapy with the results obtained in this study.     

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

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

Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer.

BACKGROUND: Since 1990, we have treated patients with advanced nasopharyngeal cancer with induction chemotherapy and concomitant chemoradiotherapy. We herein report the results of our experience. PATIENTS AND METHODS: From 1990 to 1999, 27 patients with locoregionally advanced nasopharyngeal cancer were treated with induction chemotherapy followed by concomitant chemoradiotherapy. Using the American Joint Committee on Cancer's 1992 stage classification, all patients were stage III (11%) or IV (89%). By histology, 63% were poorly differentiated carcinoma and 37% squamous cell carcinoma. The median age was 42 years. Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin and interferon-alpha2b were administered, followed by concomitant chemoradiotherapy consisting of seven cycles of 5-fluorouracil, hydroxyurea and once-daily radiotherapy (FHX) on a week-on week-off schedule. The median radiotherapy dose was 70 Gy. RESULTS: Clinical response to induction chemotherapy was 100%, 54.2% complete response (CR) and 45.8% partial response. Clinical and/or pathological (37% of all patients had post-treatment biopsy with or without neck dissection) CR after FHX was 100%. At a median follow-up of 52 months, three failures were observed. Two patients have died of disease, one of local failure and one of distant metastases. One patient is alive with an isolated rib metastasis. At 5 years, actuarial locoregional control is 93% and actuarial distant control 92%. The overall survival at 3 and 5 years is 88% and 77%, respectively. Four patients died of unrelated illnesses and had no evidence of disease with respect to their nasopharyngeal cancer. The progression-free survival at 3 and 5 years is 92% and 86%, respectively. Thirty-three per cent of patients required a reduction in the chemotherapy dose due to acute toxicity. Chronic toxicity was not observed, with all patients able to eat orally without dietary restrictions. CONCLUSIONS: Treatment of locoregionally advanced nasopharyngeal cancer with induction chemotherapy followed by concomitant chemoradiotherapy resulted in excellent overall survival with acceptable toxicity. These results are encouraging and warrant further investigation of intensified approaches.     

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.     

Treatment results of concurrent chemoradiotherapy with CDDP or CDGP plus 5-FU for carcinoma of the oropharynx and hypopharynx

Twenty-eight patients with oropharyngeal or hypopharyngeal carcinoma received concurrent chemoradiotherapy with CDDP or CDGP plus 5-FU between January 2001 and April 2006. The numbers of patients according to clinical stage were stage II:2; stage III:5; stage IVa:19 ; and stage IVb:2. Total radiation dose was 60-73.8 Gy (median 66 Gy) and overall treatment time was 41-57 days (median 47 days). Two courses of 5-FU 700 mg/m(2) on days 1-5 and CDDP or CDGP 70 mg/m(2) on day 4 were administered concurrently with radiotherapy. Median follow-up period was 26 months (range, 8-64 months).The incidences of grade 3 or greater acute toxicity were leukopenia 29%, anemia 21%, thrombocytopenia 7%, pharyngeal mucositis 43% and nausea 14%. No severe late toxicity was observed. Treatment responses of primary lesions were CR in 24 patients (86%) and PR in 4 patients (14%). The two-year local control rate was 87% and the 2-year overall survival rate was 72%. Concurrent chemoradiotherapy with CDDP or CDGP plus 5-FU seemed to be effective for advanced carcinomas of the oropharynx and hypopharynx.     

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy

PURPOSE: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. METHODS AND MATERIALS: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). RESULTS: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. CONCLUSION: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.     

同期放化疗对侵犯气管的局部晚期食管癌的疗效观察

目的　探讨同期放化疗对晚期食管癌侵及气管的临床疗效。方法　收集经病理检查确诊的１６８例食管癌侵及气管病例,其中７３例采取单纯放射治疗（单放组）,以６／１５ＭＶＸ线常规外照射,１.８Ｇｙ／次,５次／周,照射总剂量６１.２～６４.８Ｇｙ;９５例患者行化放疗治疗（化放组）,予顺铂（ＤＤＰ）联合氟尿嘧啶（５-ＦＵ）方案化疗（ＤＤＰ２０ｍｇｄ１～ｄ５,５-ＦＵ５００ｍｇ／ｍ２ｄ１～ｄ５）４个周期,２８天为１周期,于第２周期化疗开始时行同期放疗,放疗方案同单放组。观察两组的近期疗效、毒副反应和远期疗效。结果　化放组的有效率（ＲＲ）为６５.３％,高于单放组的４５.２％（Ｐ＝０.００９）;化放组较单放组ＫＰＳ评分提高更显著（Ｐ＝０.００４）。化放组的３年生存率为１７.９％,高于单放组的６.９％（Ｐ＝０.０３５）。两组主要毒副反应包括急性放射性食管炎、放射性气管炎和白细胞减少,化放组的白细胞减少发生率高于单放组（Ｐ＝０.０２２）。结论　同期放化疗对晚期食管癌侵及气管患者较单纯放射治疗的近期疗效好,明显改善患者的生活质量,生存时间延长,且相对安全。     

同步放化疗与序贯放化疗治疗中晚期食管癌的临床研究

目的 比较同步放化疗与序贯放化疗治疗中晚期食管癌的近期疗效和长期生存率.方法 168例中晚期食管癌患者随机分为两组:同步放化疗组91例;序贯放化疗组77例.同步放化疗组:放疗2 Gy/次,总量50～ 56 Gy.同步化疗2周期,放疗结束后继续化疗4周期;序贯放化疗组:放疗2 Gy/次,总量60 ～64 Gy.待放疗结...     

≥70岁食管癌根治性3DRT±化疗预后分析

目的 探讨根治性3DRT±化疗在≥70岁食管癌患者中的疗效和不良反应。方法回顾分析2008—2013年收治的116例接受根治性3DRT±化疗的≥70岁食管癌患者,其中同期放化疗32例、序贯放化疗24例、单纯放疗60例。Kaplan-Meier法计算OS、PFS率并Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 随访率100%。2、3年样本量分别为102、77例。1、2、3年OS率分别为59.1%、38.4%、23.2%,PFS率分别为61.9%、37.9%、0%。同期放化疗、序贯放化疗、单纯放疗的中位OS分别为22.3、18.0、12.4个月(P=0.044);放疗60 Gy、<60 Gy的中位OS分别为24.7、10.9个月(P=0.036),60 Gy、>60 Gy的中位OS分别为24.7、18.7月(P=0.938)。多因素分析显示性别、是否联合化疗及放疗剂量为OS的影响因素(P=0.003、0.042、0.037)。结论 老年食管癌能耐受根治性3DRT±化疗且可取得与<70岁患者相似疗效,根治性同期放化疗预后优于序贯放化疗及单纯放疗,放疗60 Gy较<60 Gy可明显提高生存,60 Gy为最适宜的放疗剂量。     

Non-randomized clinical study comparing chemotherapy plus radiotherapy with radiotherapy alone in neoadjuvant therapy for oral cancer

Neoadjuvant therapy plays an important role for organ preservation and survival rate in the treatment of oral cancer. We clinically compared the effect of neoadjuvant radiotherapy and chemoradiotherapy in patients with oral cancer. We retrospectively examined 47 patients diagnosed with oral squamous cell carcinoma who underwent neoadjuvant therapy followed by curative surgery in the oral and maxillofacial surgery department of Ehime University Hospital. We divided them into two groups: radiotherapy alone (24 cases) and chemoradiotherapy (23 cases). The patients in the radiotherapy group underwent irradiation of 32.6 +/- 5.0 Gy (mean +/- SD). The patients in the chemoradiotherapy group received a low-dose fraction of cisplatin (8 mg/mm2/day, 5 days a week; total dose: 139.4 +/- 67.1 mg) and 5-fluorouracil (300 mg/mm2/day, 5 days a week; total dose: 5,900 +/- 1,839.8 mg) combined with simultaneous irradiation of 31.0 +/- 3.2 Gy. None of the 24 patients had a complete response to radiotherapy alone and 12 (50%) had a partial response. Six (26%) of the 23 patients had a complete response to chemoradiotherapy and 12 (52%) had a partial response. The primary control rate (82.6%) to chemoradiotherapy was higher than that (67.5%) to radiotherapy alone although no significant difference was found. The 5-year survival rate was 64.3% in the radiotherapy group and 62.8% in the chemoradiotherapy group. The findings of the present study suggest that while the combination of radiation and cisplatin/5-fluorouracil in neoadjuvant therapy for oral cancer may not bring a significant benefit to improve survival rate, the primary local control rate is improved in comparison with radiotherapy alone.     

Evaluation of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer. We performed an intra-arterial infusion chemotherapy (5-FU was injected continuously: 250 mg/day/body x 28 days, CDDP was injected weekly: 5 mg/day x 5 days) associated with radiotherapy (2-3 Gy/day x 20-30 days) for local recurrence of rectal cancer with the aim of pain-relief. Both patients markedly tended to feel less pain after the radiotherapy. Radiotherapy has been useful for pain-relief of the localized bone metastasis. The present intra-arterial infusion chemotherapy associated with radiotherapy was a possible local therapy for local recurrence of rectal cancer in the pelvis. Although the survival benefit depends on the presence of other site of recurrence, this procedure is useful for the improvement of QOL by relieving the pain of the patients.     

Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: evidence of a radiation and chemotherapy dose response.

BACKGROUND AND PURPOSE: Numerous trials have shown that pathological complete response (pCR) following preoperative chemoradiotherapy (CRT) and surgery for oesophageal cancer is associated with improved survival. However, different radiotherapy doses and fractionations and chemotherapy drugs, doses and scheduling were used, which may account for the differences in observed pCR and survival rates. A dose-response relationship may exist between radiotherapy and chemotherapy dose and pCR. PATIENTS AND METHODS: Trials using a single radiotherapy and chemotherapy regimen (5FU, cisplatin or mitomycin C-based) and providing information on patient numbers, age, resection and pCR rates were eligible. The endpoint used was pCR and the covariates analysed were prescribed radiotherapy dose, radiotherapy dosexdose per fraction, radiotherapy treatment time, prescribed chemotherapy (5FU, cisplatin and mitomycin C) dose and median age of patients within the trial. The model used was a multivariate logistic regression. RESULTS: Twenty-six trials were included (1335 patients) in which 311 patients (24%) achieved pCR. The probability of pCR improved with increasing dose of radiotherapy (P=0.006), 5FU (P=0.003) and cisplatin (P=0.018). Increasing radiotherapy treatment time (P=0.035) and increasing median age (P=0.019) reduced the probability of pCR. The estimated alpha/beta ratio of oesophageal cancer was 4.9 Gy (95% confidence interval (CI) 1.5-17 Gy) and the estimated radiotherapy dose lost per day was 0.59 Gy (95% CI 0.18-0.99 Gy). One gram per square metre of 5FU was estimated to be equivalent to 1.9 Gy (95% CI 0.8-5.2 Gy) of radiation and 100mg/m2 of cisplatin was estimated to be equivalent to 7.2 Gy (95% CI 2.1-28 Gy). Mitomycin C dose did not appear to influence pCR rates (P=0.60). CONCLUSIONS: There was evidence of a dose-response relationship between increasing protocol prescribed radiotherapy, 5FU and cisplatin dose and pCR. Additional significant factors were radiotherapy treatment time and median age of patients within the trial.     

The role of low dose cisplatin plus 5-fluorouracil for treatment of recurrent and/or advanced squamous cell carcinoma of the head and neck

To improve survival rate in advanced head and neck cancer, we scheduled 90 patients to receive low dose cisplatin plus 5-fluorouracil regimen as neoadjuvant(NAC), concurrent(CC), adjuvant(AC), and second line chemotherapy (SC) setting. Our regimen consisted of cisplatin (CDDP 5 mg/m2/1 hr infusion on days 1-5, 8-12, 15-19, 22-26) and 5-fluorouracil (5-FU 200 mg/m2/24 hr infusion or oral administration of tegaful-uracil (UFT-E) 400 mg/body on days 1-28). The concurrent chemoradiotherapy consisted of conventional irradiation with 1.6-2.0 Gy/day on five days per week up to a total dose around 60Gy, and CDDP 3 mg/m2 by intravenous infusion over 1 hour plus 5-FU 150 mg/m2 by intravenous infusion over 24 hours per day on five days per week. For SC, 24 patients evaluable for response, 4 CR and 6 PR with RR of 42% were achieved. For NAC, 14 patients were evaluated for response, 2 CR and 7 PR were achieved. CC was indicated for locally unresectable cases. Of the 33 patients evaluable for response were 17 CR and 9 PR with RR of 79%. Dose limiting toxicities for chemotherapy were anemia and leukopenia and chemoradiotherapy was mucositis. Our treatment modality showed marginal toxicity and good response. Moreover, our regimen could be given in an outpatient setting safely so quality of life for patients was identical. We concluded that for advanced head and neck cancer, these treatment options were effective for second line and adjuvant setting. Chemoradiotherapy with this regimen also gave a impact for improving local control and survival period for locally unresectable cases.     

Feasibility study of single agent Cisplatin and concurrent radiotherapy in Japanese patients with squamous cell carcinoma of the head and neck: preliminary results

BACKGROUND: Concurrent chemoradiotherapy with the single agent cisplatin (CDDP + RT) has been recognized worldwide as the standard treatment for unresectable locally advanced SCCHN. The objective of this study was to clarify the feasibility of CDDP + RT in Japanese patients. Patients and methods Patients with unresectable squamous cell carcinoma of the head and neck were given single daily fractionated radiation (70 Gy at 2 Gy/day) and chemotherapy consisting of a 2 h infusion of CDDP 100 mg/m(2) on days 1, 22 and 43. The primary endpoint was the rate of completion of CDDP + RT. RESULTS: Between November 2005 and January 2007, 20 patients were enrolled, 19 males and one female with a median age of 61.5 years (range 50-74). One patient had recurrent unresectable disease after surgery and the remaining 19 had stage IV disease. No grade 4 hematologic toxicities were observed. The incidence of grade 3 mucositis was 55% and no treatment-related death occurred. Full-dose irradiation was performed in all patients, with a median duration of radiotherapy of 50 days (range 48-54). Although all patients received the first two administrations of CDDP, the third dose was administed in 17 patients (85%). The rate of completion of CDDP + RT was 85% and the dose intensity of CDDP was 28.9 mg/m(2)/week (relative dose intensity 89%). Overall complete response rate was 50% and the rate of primary complete response was 90%. CONCLUSION: Concurrent chemoradiation therapy with the standard dose of CDDP is feasible in Japanese patients. Treatment modification based on racial differences is not necessary.     

Alternating chemotherapy and accelerated split-course irradiation in locally advanced nonsmall cell lung carcinoma.

BACKGROUND: The prognosis of patients with locally advanced nonsmall cell lung carcinoma (NSCLC), which is usually unresectable, is very poor, and patient survival rarely reaches 1 year. However, prolonged survival correlated with objective responses has been observed among patients with intrathoracic disease treated with a combination of cytotoxic drugs and local irradiation despite the lack of consensus regarding the schedule of such combined therapy. From October 1989 to November 1993, a Phase II study was conducted to evaluate the tolerability and efficacy of alternating chemotherapy and accelerated split-course radiotherapy in the treatment of patients with locally advanced NSCLC. METHODS: Sixty-three consecutive patients with unresectable Stage III NSCLC entered this study. The treatment was composed of 3 cycles of combined chemotherapy and radiotherapy at 4-week intervals. Chemotherapy with cisplatin (30 mg/m2/day) and etoposide (100 mg/m2/day) was delivered intravenously on Days 1, 2, and 3, followed by radiotherapy on Days 4-8. A course of radiotherapy consisted of 1.5 gray (Gy) per fraction twice a day (3 Gy per day) for 5 consecutive days, for a total dose of 15 Gy. Response was assessed after 3 courses, for a total irradiation dose of 45 Gy. In cases of objective antitumoral response with operable tumor, surgery was performed. A fourth course of chemotherapy and radiotherapy, for a total dose up to 60 Gy in 12 weeks, was administered to all patients. Two additional courses of chemotherapy were given, for a total of six. RESULTS: Of the 63 patients, 62 were evaluable for response. Six had a complete remission and 36 a partial response, resulting in an overall response rate of 67.7%. Nine patients underwent surgery (pneumonectomy for seven patients and lobectomy for two patients), and the complete disappearance of any residual tumor was documented histologically in four. Of the 290 chemotherapy courses delivered, there were 31 of Grade 3-4 toxicity, mainly leukopenia and vomiting. The median times of freedom from disease progression and overall survival were 8 months (confidence interval [CI], 7-9.5) and 14 months (CI, 10-22), respectively. The 1-, 2-, and 5-year survival rates of the 62 patients were 54%, 35%, and 21%, respectively. Patients who responded had a significantly longer median survival (16 months) than nonresponders (7 months) (P = 0.02). However, there was no difference in the survival of resected and nonresected patients. CONCLUSIONS: This treatment schedule resulted in a high response rate with prolonged survival. However, the toxicity of this approach was not negligible, even though it did not preclude this strategy. This combined modality must be compared with other combinations of alternating or sequential chemoradiotherapy.     

早期鼻咽非霍奇金淋巴瘤:不同免疫表型的预后差异和治疗对策分析

背景与目的:鼻咽是淋巴瘤较常见的发病部位之一,但对于不同病理免疫表型(B细胞与NK/T细胞)鼻咽淋巴瘤的临床特点和预后以及相应的治疗对策的区别,临床报道较少。本研究的目的在于探讨不同免疫表型的早期鼻咽非霍奇金淋巴瘤的临床表现和治疗效果,评估B细胞和NK/T细胞表型之间的预后差异,为治疗方案的相应调整提供依据。方法:回顾性分析1987年5月至2003年12月间80例初治的早期鼻咽非霍奇金淋巴瘤患者的临床资料,病理和免疫表型检查显示48例为B细胞来源(B组),32例为T和NK细胞来源(T组)。42例患者接受化放疗综合治疗,31例单纯化疗,7例单纯放疗。化疗多数采用标准CHOP方案,1～10周期(中位数5周期);放射治疗采用高能光子射线配合高能电子线,常规分割,照射剂量DT30～70Gy(中位数52Gy)。两组患者的治疗方式相近,但B组的化疗周期数大于后者。结果:B组和T组的5年总生存(OS)率分别为69.5%和35.5%(P=0.003),5年无疾病进展生存(PFS)率分别为53.3%和28.9%(P=0.032)。多因素分析显示,B细胞免疫表型、无全身症状、局部控制是OS有利的独立预后影响因素;B细胞免疫表型、治疗反应好(CR/PR)是PFS有利的独立预后因素。治疗方法影响OS的单因素分层分析显示:B组患者单纯化疗(19例)和放化疗综合治疗(25例)的5年OS分别为68.1%、61.7%,单纯放射治疗的4例随访期间全部生存(P=0.311);而T组患者单纯化疗(12例)和放化疗综合治疗(17例)的5年OS分别为0、44.1%,单纯放射治疗的3例中2例生存4、10个月后死亡,1例随访60个月生存(P=0.020)。结论:早期鼻咽非霍奇金淋巴瘤病例中,虽然B细胞表型患者的年龄偏大、颈淋巴结受侵比例偏高,其预后却优于NK/T细胞表型患者。后者全身症状多见,单纯化疗的缓解率和生存率较低,在综合治疗中应该更积极配合放射治疗。