Raltitrexed plus radiotherapy for the treatment of unresectable/recurrent rectal cancer: a phase I study.

BACKGROUND: Current consensus is that a combination of radiotherapy and chemotherapy may provide the optimal treatment for patients with unresectable rectal cancer. Raltitrexed has proven efficacy in the treatment of advanced colorectal cancer and has an acceptable toxicity profile. The aim of this phase I study was to determine the recommended dose of raltitrexed in combination with radiotherapy in patients with unresectable/recurrent rectal cancer. PATIENTS AND METHODS: Patients were treated with radiotherapy (25 fractions at 2.0 Gy per fraction) five times per week for 5 weeks. Raltitrexed was administered on days 1 and 22 at 2.0, 2.6 and 3.0 mg/m(2). RESULTS: A total of 20 patients were entered into the study. Dose-limiting toxicities were recorded in three of 20 patients following the first dose of raltitrexed; one patient at 2.6 mg/m(2) (grade 3 diarrhoea, grade 3 neutropenia and grade 2 pyrexia) and two patients at 3.0 mg/m(2) (one grade 3 neutropenia and one grade 4 diarrhoea). The most common non-haematological and haematological treatment-related adverse events were diarrhoea (11 of 20, two grade 3, one grade 4) and leukopenia (eight of 20, one grade 3, one grade 4), respectively. CONCLUSIONS: The recommended dose of raltitrexed in combination with radiotherapy for future studies is 2.6 mg/m(2).     

Oxaliplatin with raltitrexed and preoperative radiotherapy in T3-T4 extraperitoneal rectal cancer. A dose finding study

AIMS AND BACKGROUND: The availability of new drugs offers the opportunity to improve the outcome of locally advanced rectal cancer. Raltitrexed and oxaliplatin are effective in advanced colorectal cancer with acceptable toxicity and can act as radiation enhancers as shown in phase I-II studies. The aim of the study was thus to determine the recommended dose of oxaliplatin concomitantly administered with raltitrexed and concurrent preoperative radiotherapy in patients with stage II-III extraperitoneal rectal cancer. METHODS: From September 2001 to September 2002, 18 consecutive patients with T3/T4 rectal cancer were treated at our Institution with preoperative chemoradiation followed by surgery after 6-8 weeks. Pelvic radiotherapy was delivered at a dose of 45 Gy in 25 fractions in 5 weeks followed by a 5.4 Gy boost at 1.8 Gy daily. Concomitant chemotherapy consisted of 3 mg/m2/i.v. of raltitrexed on days 1, 19, 38 of radiotherapy treatment with incremental doses of oxaliplatin according to dose finding rules (4 dose levels: 65, 85, 110, 130 mg/m2). Dose-limiting toxicity for oxaliplatin was defined as either grade 3-4 hematological or grade 3-4 gastrointestinal or neurological toxicity. We studied a minimum of 3 patients at each dose level. RESULTS: Three patients were treated at 65, 85, and 110 mg/m2/i.v., respectively, while 9 patients were recruited at the last dose level. Neither grade 3-4 gastrointestinal nor neurological toxicity were documented. Dose-limiting toxicity was documented in 2/9 subjects at the 130 mg/m2 level consisting of grade 3 transient asymptomatic leukopenia. Thirteen patients developed transient increase of one or more liver enzymes (grade 3-4) and 2 patients developed grade 3 perineal dermatitis. All patients received the programmed dose of radiotherapy. The chemotherapy regimen was not completed in 4 cases due to grade 2 protracted leukopenia. CONCLUSIONS: The maximum tolerated dose of oxaliplatin was not reached at the maximum dose level (i.v.); 130 mg/m2 can therefore be defined as the recommended dose. The combination of oxaliplatin with raltitrexed and radiotherapy can be considered feasible and well tolerated.     

Results of a phase I study to determine the maximum tolerated dose of capecitabine when given concurrently with radical radiotherapy in the treatment of squamous cell carcinoma of the head and neck.

Capecitabine is preferentially converted to 5-fluorouracil within tumours, exploiting the higher levels of thymidine phosphorylase (TP) found in areas of poor perfusion and hypoxia. In addition radiation leads to up regulation of TP expression. To exploit these advantages of capecitabine as a synchronous chemoradiotherapy agent patients with advanced squamous cell carcinoma of the head and neck were recruited into a phase I non-randomised dose finding study. Capecitabine was given twice daily, 7 days a week at a dose starting at 350 mg/m(2) bid. Radiotherapy using a beam directed technique was prescribed to 55 Gy in 20 fractions over 4 weeks. A total of 24 patients were treated. Dose-limiting toxicity (grade IV mucositis) was reached at a capecitabine dose of 550 mg/m(2) bid. Radiotherapy was completed without delay in all cases. There was no systemic drug related toxicity. Capecitabine offers the prospect of an orally administered drug for use synchronously with radiotherapy, which in doses up to 500 mg/m(2) bid is well tolerated.     

Phase I study of weekly docetaxel infusion and concurrent radiation therapy for head and neck cancer

OBJECTIVE: This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel in combination with concurrent radiotherapy for treating head and neck cancer. METHODS: Twelve patients with unresectable or postoperative head and neck cancers were enrolled in a dose-escalating phase I study. Eleven of the 12 patients were postoperative patients with intermediate or high pathological risk features. Radiotherapy was delivered as a standard fractionation regimen (2 Gy/day, 5 fractions/week) to a total dose of 60-70 Gy. The starting dose of docetaxel was 10 mg/m(2) (once per week) with a subsequent dose escalation of 5 mg/m(2) in cohorts of three patients. In 2001 and 2002, 12 patients completing three dose levels were included in the study. RESULTS: The MTD of docetaxel was 20 mg/m(2). With the third dose level (20 mg/m(2)), DLT was observed in two of three patients. One experienced grade IV mucositis and another suffered from prolonged grade III mucositis-enforced treatment delay for 13 days. Hematological toxicity was minimal. Mucositis was the DLT of concurrent chemoradiotherapy using weekly docetaxel administration for head and neck cancer. CONCLUSIONS: We identified the recommended phase II dose of docetaxel as 15 mg/m(2) administered weekly with concurrent radiotherapy for head and neck cancers.     

Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study

The use of raltitrexed ('Tomudex') as concomitant chemotherapy during preoperative radiotherapy in chemona?ve patients with stage II/III rectal cancer has been examined in this study and its recommended dose in conjunction with radiotherapy investigated. Forty-five Gray (Gy) of radiotherapy (1.8 Gy daily, 5 days per week) was delivered to the posterior pelvis, followed by a 5.4 Gy boost. Single doses of raltitrexed (2.0, 2.5 and 3.0 mg/m(2)) were administered on days 1, 19 and 38. Only 1 of the 15 patients entered experienced a dose limiting toxicity (DLT) (grade 3 leucopenia) at the 3.0 mg/m(2) dose level. The overall response rate was 80% (five complete responses, seven partial responses). These preliminary data suggest that raltitrexed is a well tolerated and effective treatment when combined with preoperative radiotherapy in patients with stage II/III rectal cancer. The recommended dose of raltitrexed for future phase II studies will be 3.0 mg/m(2).     

Complete response in a case of advanced esophageal cancer treated by combined chemotherapy of TS-1 and CDDP with radiotherapy

A 70-year-old patient with advanced esophageal cancer with invasion to the aorta was treated by combined chemotherapy of TS-1 and CDDP with radiotherapy. TS-1 (80 mg/m2) was administered for 14 days followed by 14 days rest, CDDP (70 mg/m2) was administered by 24 h continuous intravenous infusion at day 8 after the start of TS-1. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy for 3 weeks. After the end of the first course, leukocytopenia of grade 2 and thrombocytopenia of grade 2 were observed. The second course of chemoradiotherapy was suspended for 1 week. After recovery from the toxicity, the second course was started. After the 2 courses of chemoradiotherapy, endoscopic examination with biopsy revealed the disappearance of the esophageal cancer. Combined chemotherapy of TS-1 and CDDP was administered 2 times after chemoradiotherapy. After this therapy, endoscopy and a CT showed a complete clinical response. No severe adverse effects were observed during this therapy. Combined chemotherapy of TS-1 and CDDP with radiotherapy can be effective for advanced esophageal cancer.     

A Phase I study of raltitrexed and paclitaxel given every 3 weeks to patients with solid tumors.

BACKGROUND: Raltitrexed is a novel thymidylate synthase inhibitor with single agent activity in colorectal, nonsmall cell lung, and breast carcinomas. The recommended Phase II dose of raltitrexed administered as a single agent is 3 mg/m2 every 3 weeks. Paclitaxel also has a broad spectrum of activity. A Phase I study of both agents in combination therapy was conducted. METHODS: Eligible patients had refractory solid tumors and a Cancer and Leukemia Group B performance status of 0 to 2. Cohorts of patients were treated with escalating doses of raltitrexed as a 15-minute intravenous infusion immediately followed by 175 mg/m2 of paclitaxel administered over 3 hours. Dose-limiting toxicity was defined as World Health Organization Grade 4 neutropenia with fever, Grade 4 thrombocytopenia requiring platelet transfusion, a nonhematologic toxicity of Grade 3 or higher (excluding nausea, emesis, and alopecia), or failure of toxicities to recover to Grade 1 or lower within 21 days after causing a dose delay. RESULTS: A total of 33 patients enrolled in the study. Raltitrexed was escalated in increments of 0.5 mg/m2, from 0.5 mg/m2 to the recommended Phase II dose of 3 mg/m2. Dose-limiting toxicity first was observed at a raltitrexed dose of 2 mg/m2. At a dose of 3 mg/m2, dose-limiting neutropenia was observed in 2 of 12 patients. Diarrhea was the other dose-limiting toxicity. Two patients achieved a partial response (one patient with carcinoma of the head and neck and another with gallbladder carcinoma). CONCLUSIONS: The authors conclude that raltitrexed and paclitaxel may be administered in combination at their respective single agent Phase II doses. Phase II testing of this combination is indicated.     

Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study

To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36 Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30 Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500 mg/m²/120 h was intravenously administered for 5 days (Days 1–5), and NDP at 120 mg/m²/6 h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert’s formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.     

Raltitrexed and radiotherapy as adjuvant treatment for stage II-III rectal cancer: a feasibility study

AIMS AND BACKGROUND: Adjuvant 5-FU chemotherapy plus radiotherapy represents the standard treatment for radically resected rectal cancer at high risk of relapse according to the NIH Consensus Conference. The therapeutic gain was obtained with a high rate of severe treatment-related toxicity and a suboptimal patient compliance with this regimen. Raltitrexed is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable toxicity and radiosensitizing properties, as the published phase I trials in combination with radiotherapy have shown. The aim of this prospective multicenter phase II study was to evaluate the feasibility, gastrointestinal and hematological acute toxicity of raltitrexed in combination with radiotherapy in rectal cancer patients. METHODS: From September 2000 to June 2004, 50 patients with radically resected stage II-III rectal adenocarcinoma were treated. All patients were evaluable for compliance and acute toxicity. Within 45-60 days of surgery, each patient underwent concomitant adjuvant radiochemotherapy. Radiotherapy was administered to the pelvis (plus perineum after abdominoperineal resection) with photon beam energy exceeding 5 MV, 3-4 fields, 45 Gy/25 fractions/5 weeks plus a boost delivered to the site of resected disease with 3-4 fields, 9 Gy/5 fractions/1 week to a total dose of 54 Gy. The boost dose was administered after complete exclusion of the small bowel from the treatment volumes; if this was not possible a total dose of 50.4 Gy was given. Raltitrexed was administered intravenously at a dose of 3 mg/m2 as a bolus injection on days 1 and 22 of radiotherapy one hour before treatment, for a total of two cycles. Each patient underwent weekly clinical evaluation and laboratory tests. Toxicity was assessed by the WHO scale. RESULTS: Forty-five (90%) patients completed the established treatment. Acute severe toxicity included grade III proctitis in 4/50 (8%), grade III-IV diarrhea in 4/50 (8%), grade III perineal dermatitis in 4/50 (8%) and grade III leukopenia in 2/50 (4%) patients; five patients (10%) experienced a transient grade Ill increase in their liver biochemistry values. CONCLUSIONS: Our data related to acute toxicity and patient compliance proved the feasibility of this adjuvant radiochemotherapy treatment. A longer follow-up is necessary to evaluate the effectiveness of this new regimen in terms of disease-free and overall survival.     

Raltitrexed (Tomudex) in combination with platinum-based agents and/or anthracyclines: preliminary results of phase I clinical trials

Three ongoing, dose-escalation, phase I studies are evaluating the combination of raltitrexed with oxaliplatin or anthracyclines (with and without cisplatin). In study 1, patients with advanced solid tumours received 2.0-3.75 mg/m2 raltitrexed, followed 45 min later by 85-130 mg/m2 oxaliplatin (2-h infusion) every 3 weeks. In study 2, patients with advanced oesophageal or gastric adenocarcinoma received 2.0-3.0 mg/m2 raltitrexed with 50 mg/m2 intravenous (i.v.) epirubicin and 60 mg/m2 i.v. cisplatin every 3 weeks. In study 3, patients with advanced or metastatic gastric cancer received 2.5-3.5 mg/m2 raltitrexed followed by 30-60 mg/m2 i.v. doxorubicin every 3 weeks. In all studies, raltitrexed was given as a 15-min infusion. All the combinations evaluated were administered in convenient 3-weekly schedules and were generally well tolerated. Recommended doses for raltitrexed and oxaliplatin are the same in combination as for single-agent use, i.e. 3.0 mg/m2 raltitrexed and 130 mg/m2 oxaliplatin. The recommended dose of raltitrexed in combination with cisplatin and epirubicin is 2.5 mg/m2. No dose-limiting toxicities were observed during co-administration of the full single-agent doses of raltitrexed and doxorubicin (3.0 mg/m2 and 60 mg/m2, respectively); dose escalation is continuing. Preliminary efficacy results were encouraging, particularly for the combination of raltitrexed and oxaliplatin in patients with mesothelioma and advanced colorectal cancer. Preliminary data from these phase I studies suggest that the combination of raltitrexed with platinum-based agents and/or anthracyclines may represent useful regimens for the treatment of patients with advanced cancer. Further studies are required to identify the most effective combinations of raltitrexed with both established and new anticancer agents.     

Raltitrexed: current clinical status and future directions.

Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC), and has single-agent activity in a variety of advanced solid tumours. Although both raltitrexed and 5-FU are thymidylate synthase inhibitors, raltitrexed has a specific mode of action and a toxicity profile distinct from 5-FU. The mechanism of action of raltitrexed is also completely different from that of oxaliplatin, irinotecan and other drugs with which it has been combined. These properties, together with preclinical data, suggested that combinations of raltitrexed with 5-FU, other chemotherapeutic agents, or radiotherapy could result in improved therapies for a variety of advanced solid tumours, including advanced CRC. This review outlines the appropriate management of patients treated with raltitrexed, whether as monotherapy or in combination, and discusses the preliminary results of combination studies with raltitrexed in a range of tumour types including advanced CRC, malignant mesothelioma, gastric, pancreatic, head and neck, and non-small-cell lung cancers. Of particular interest is the combination of raltitrexed and oxaliplatin, which has shown promising antitumour effects in first-line treatment of advanced CRC and malignant mesothelioma, a disease that is refractory to chemotherapy.     

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.     

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.     

Concomitant Chemoradiotherapy for Advanced Head and Neck Cancer

Head and neck cancer is mostly curable in the early stages byeither surgery or radiotherapy alone, but the control rate foradvanced stages is low, even with combined surgery and postoperativeradiotherapy. From September, 1990, to January, 1992, 35 patientswith locoregionally advanced head and neck cancers were enteredin a prospective study of concomitant chemoradiotherapy. Thirty-threecompleted the treatment. There were 29 males and four femaleswith a median age of 53 years. All except one patient were instage IV. Radiotherapy was delivered using a telecobalt unitand by conventional fractionation (1.8 Gy/fraction, 5 fractions/wk).Chemotherapy with cisplatin (10 mg/m²/day, daily, days 1-5)and 5-FU (500 mg/m²/day continuously infused for five days)was given concurrently during the first and fifth weeks of radiation.Twenty-four among 31 eligible patients achieved complete response(77.4%) and the other seven (22.6%) partial response, resultingin a 100% response rate. The toxicities experienced were increasedcompared with those caused by radiotherapy alone. The most commonside effects were gastrointestinal and hematologic toxicitiesbut the whole treatment was well tolerated. The two-year actuarialsurvival rate is 45%. We found the primary origin and overalltreatment time to affect survival significantly. The survivalrate for tumors arising from the nasopharynx or paranasal sinusis better than for those arising from other regions of the headand neck. The shorter treatment times (within eight weeks) hada better survival rate. Our preliminary experience suggeststhat concomitant chemoradiotherapy is both feasible and effectivefor head and neck cancer. The optimal scheduling and dosageof concomitant chemoradiotherapy should be further researched.     

局部晚期宫颈癌同步放化疗临床观察

目的探讨同步放化疗治疗局部晚期宫颈癌的疗效和不良反应。方法 80例经病理确诊、临床分期为Ⅱb~Ⅲb期局部晚期宫颈癌患者随机分成两组,每组各40例,均予根治性放疗,体外放疗均采用直线加速器15 MV X射线,DT46~50 Gy,腔内治疗采用192Ir后装机,A点6 Gy/周,总剂量为36~42 Gy。两组放疗方法相同,同步放化疗组在放疗前每周日加用多西紫杉醇(希存)40 mg静滴,共6周。观察近期疗效、3年生存率及放化疗并发症。结果放疗后3个月同步放化疗组有效率(100%)明显高于单纯放疗组72.5%(P<0.05),局部复发率、远处转移率两组分别为5.0%、2.5%和17.5%、15.0%,差异有统计学意义(P<0.05);3年生存率分别为82.5%和55.0%(P<0.05),而毒副作用无明显增加(P>0.05)。结论同步放化疗能提高局部晚期宫颈癌患者的疗效及生存率,降低局部复发率及远处转移率。     

放疗联合雷替曲塞奥沙利铂同步治疗中晚期食管癌的Ⅱ期临床研究

  目的   初步评价中晚期食管癌患者应用雷替曲塞/奥沙利铂同步放疗的疗效、安全性。   方法   54例采用食管癌非手术分期的Ⅱ~Ⅲ期食管癌患者,应用雷替曲塞/奥沙利铂方案联合放疗进行治疗。放疗剂量60 Gy/30次。雷替曲塞剂量为2.6 mg/m2,奥沙利铂剂量为100 mg/m2,均于放疗d1、d22应用。放疗期间行2周期化疗。   结果   全组共9例（16.7%）获得完全缓解,部分缓解37例（68.5%）,无缓解或病情进展8例（14.8%）,有效率85.2%。1、2年局部控制率分别为75.4%和57.3%,1、2年生存率分别为70. 4%（95%CI:0.6~0.8）、46.6%（95%CI:0.3~0.6）。患者的急性放射性食管炎、白细胞下降、急性腹泻、神经毒性发生率分别为100%、72.2%、16.7%、44.4%;不良反应≥3级分别为7.4%、7.4%、1.9%、0。   结论   雷替曲塞联合奥沙利铂同步放疗对提高中晚期食管癌临床缓解率、生存率有一定意义,且不良反应轻,值得进一步大样本Ⅲ期临床研究。      

Raltitrexed (Tomudex) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies

Radiotherapy, either alone or in combination with chemotherapy, may reduce local recurrence of rectal cancer following surgery and improve survival of patients with operable and advanced/recurrent/inoperable disease. Chemotherapy with 5-fluorouracil in combination with radiotherapy has been used both before and after surgery; however, the optimum schedule is unclear. In addition, alternative chemotherapy with raltitrexed (Tomudex) may be more convenient and better tolerated. The preliminary results of three phase I dose-finding studies are described, combining escalating doses of raltitrexed with radiotherapy as pre- or postoperative treatment for operable rectal cancer or as treatment for advanced/inoperable/recurrent rectal cancer. The recommended dose of raltitrexed when combined with adjuvant radiotherapy is likely to be 2.6 mg/m2. This is a small dose reduction compared with the dose of raltitrexed for the treatment of advanced colorectal cancer (3.0 mg/m2); however, toxicity appears to be lower using the pre-operative approach. Neo-adjuvant therapy with raltitrexed plus radiotherapy also demonstrated clinical activity in the pre-operative study, which showed that 22% of patients achieved a complete response and 56% a partial response. Once the recommended dose has been defined in each setting, large-scale studies will be undertaken as appropriate.     

Intra-arterial chemotherapy for head and neck cancer

There are historically speaking, three methods of intra-arterial infusion for head and neck cancer. Recently, daily concurrent chemoradiotherapy using new superselective intra-arterial infusion via superficial temporal arterial artery is noted. A catheter with a curved tip is inserted superselectively to the feeding artery of the tumor via the superficial temporal artery. Long-term catheterization is possible in this method. Thirty-five patients with stage III or IV oral cancer were treated. Radiotherapy (total dose:40 Gy/4 weeks) and superselective intra-arterial infusion chemotherapy using DOC (total dose: 60 mg/m2, 15 mg/m2/week) and CDDP total dose: 100 mg/m2, 5 mg/m2/day) were concurrently performed daily, followed by surgery. In 31 patients, intra-arterial infusion was successful(successful rate: 88.6%), and no major complication was observed. The clinical effects were CR in 25 patients(80.6%), and pathological effects of resected tumor after surgery were pathological CR in 28 (90.3%). This method promises to be new strategy of choice for the treatment of head and neck cancer.     

三维适形放疗联合雷替曲塞加奥沙利铂治疗中晚期食管鳞癌的临床观察

目的 观察三维适形放疗联合化疗治疗中晚期食管鳞癌的近期疗效和不良反应。方法 收集2011年9月至2013年4月间中晚期食管鳞癌患者42例,采用三维适形放疗联合化疗,放疗剂量：60 Gy/30次,6周完成;化疗方案为：雷替曲塞3 mg/m2,静滴,d1;奥沙利铂130 mg/m2,静滴2 h,d2,28天为1周期。放疗第1周和第5周时各化疗1周期,放疗结束后4~6周开始继续原方案巩固化疗2周期。结果 42例患者均可评价疗效,获完全缓解18例（42.9%）、部分缓解23例（54.8%）和稳定1例（2.4%）, 总有效率为97.6%。1、2年局部控制率为90.5%、71.4%, 1、2年生存率为85.7%、60.7%。全组患者的不良反应多为1~2级,急性食管炎、急性放射性肺炎、胃肠道反应、骨髓抑制及肝功能损害发生率分别为95.2%、23.8%、73.8%、42.9%和19.1%。结论 三维适形放疗联合雷替曲塞和奥沙利铂治疗中晚期食管鳞癌的近期疗效显著,局部控制率较好,毒副反应能耐受,长期疗效有待进一步观察。     

Alternating chemoradiotherapy for oropharyngeal cancer

To evaluate the usefulness of chemoradiotherapy for oropharyngeal cancer, we retrospectively analyzed disease-free survival (DFS) and acute toxicities of the patients treated with this therapy. Between 1990 and 1998, 15 patients were treated with alternating chemoradiotherapy (CRT). Chemotherapy (CT) mainly consisted of 5-fluorouracil 700 mg/m2 (i.v.) on days 1-5 and nedaplatin 100-140 mg/m2 (i.v.) on day 6. Chemotherapy was administered before the beginning of radiotherapy. One cycle of this treatment consisted of CT and a subsequent 27 to 36 Gy of radiotherapy, as a general rule, two cycles were performed. Radiotherapy was delivered in single daily fractions of 1.8 to 2 Gy, to a total dose of 54 to 75 Gy for local lesions and 45 to 86.3 Gy for nodal metastases in the neck. As a historical control, 52 patients treated with curative radiotherapy between 1971 and 1990 were analyzed and compared with the CRT group in terms of DFS. The complete response rate with CRT was 100%. The three-year DFS were 87% and 38% with CRT and RT, respectively. There was a significant difference between the two groups (p = 0.0081). The most frequent and severe acute toxicity was mucositis, with grade 3-4 occurring in 47%. Acute hematologic toxicities were mild. Therefore, this CRT is considered to be an effective and tolerable treatment, and is expected to improve survival for oropharyngeal cancer patients.