Competing causes of death in patients with locoregionally advanced head and neck cancer treated with concomitant boost radiation plus concurrent weekly cisplatin

Background

This study analyzes the morbidity and the contribution of different causes of death to the outcome of patients with locally advanced head and- neck cancer after weekly cisplatin plus concomitant boost accelerated radiation treated in our center.

Materials and methods

Ninety-four patients with locally advanced head and neck carcinoma were included in this phase II trial consisting of concomitant boost radiation plus concurrent weekly cisplatin. The 43 patients treated in our centered with long-term follow-up were analyzed. 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/m² weekly, for the first 4 weeks.

Results

Most patients (93 %) received both radiation and complete chemotherapy according to protocol. Severe late toxicity presented were subcutaneous (5 %), larynx (2 %) and esophagous (5 %). Grade I–II late toxicity included mainly xerostomy (30 %), skin (16 %) and mucosal (16 %) toxicity. With a median follow-up of 95 months (9–135), the median overall survival and progression-free survival were 26 and 19 months, respectively (95 % CI 1–52; and 95 % CI 0–45); 60 % of the patients died because of head and neck cancer and 12 % of a second neoplasm, while 27 % of non-cancer patients died.

Conclusions

Patients with locoregionally advanced head and neck cancer treated with concomitant boost accelerated radiation plus chemotherapy show significant risks of mortality from causes other than disease progression.     

Concomitant boost radiotherapy with concurrent weekly cisplatin in advanced head and neck cancers: a phase II trial.

BACKGROUND AND PURPOSE: To determine the safety and efficacy of concomitant boost radiotherapy (CBRT) with concurrent cisplatin chemotherapy (CT) in advanced head and neck cancers. PATIENTS AND METHODS: Between February 2000 and June 2001, 95 previously untreated patients of advanced head and neck cancers were treated with CBRT and concurrent cisplatin CT. CBRT consisted of: phase I--44 Gy/22fx/4.5 weeks, phase IIa--16 Gy/8fx/1.5 weeks and phase IIb--10 Gy/8fx (delivered as a second daily fraction after a gap of 6h along with phase IIa). CT (cisplatin 35 mg/m(2)) was administered weekly usually preceding CBRT by an hour. RESULTS: The median follow-up was 39 months (range 8-50 months). CBRT compliance (70 Gy in 40-44 days) was seen in 66% (63/95). Six cycles of CT was delivered in 73% (69/95). Acute grade III/IV mucosal toxicity was seen in 79% and resulted, on average, in a total weight loss of 7.9 kg from a mean pretreatment weight of 51 kg. Nasogastric tube placements were required in 26% (25/95) for an average duration of 19.3 days. Grade III leucopenia was seen in 2%. Mortality during and within 30 days of treatment was seen in 14% (13/95). Crude incidence of late subcutaneous fibrosis (grade III) was 21% (12/57) and a case of mandibular necrosis and thyroid cartilage necrosis each were seen. Initial loco regional disease clearance was seen in 59% (56/95) and the Kaplan-Meier estimates of 3-year loco-regional control rate and overall survival were 25% (median 7 months, 95% C.I. 3-11) and 27% (median 12 months, 95% C.I. 8-16), respectively. CONCLUSIONS: On present evidence, in the settings of a developing country, CBRT with concurrent cisplatin cannot be recommended as primary therapy in advanced head and neck cancers without formal comparison with other treatment modalities.     

Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck

PURPOSE: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. PATIENTS AND METHODS: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M2 and 25 mg/M2. RESULTS: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. CONCLUSIONS: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to induction chemotherapy.     

Phase II trial of gemcitabine concurrent with radiation for locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Concurrent chemoradiation is the current standard of treatment for patients with advanced unresectable head and neck squamous cell carcinoma (HNSCC). Due to the potent radiosensitizing properties of gemcitabine, we decided to assess its efficacy and toxicity with concurrent radiation in patients with advanced HNSCC. PATIENTS AND METHODS: From January 1997 to December 2001, 27 patients with locally advanced HNSCC (stage III, 37%; stage IV, 63%) were enrolled. All received a course of radiotherapy (70 Gy over 7 weeks) concurrent with weekly infusions of gemcitabine at 100 mg/m2 or 50 mg/m2. RESULTS: All patients were assessable for toxicity and 26 for response. Severe mucositis (grade 3-4) was observed in 74% of patients (grade 4, 41%). Severe hematological toxicity was uncommon. Mild and moderate xerostomy was the most common late toxicity in 23 patients (85%). The median radiation dose delivered was 70 Gy (40-80 Gy), 25 patients (93%) received > or = 80% of the intended dose. Gemcitabine dose intensity was > or = 80% in only 13 (48%) patients. The rate of complete and partial responses were 61% and 27%, respectively, for an overall response rate of 88%. At a median follow-up of 13 months (range 6-62), the actuarial 3-year progression-free survival (PFS) and overall survival (OS) were 37% and 33%, respectively. The only variable associated with prolonged survival (P = 0.0001) was the degree of response. No difference was observed in response or toxicity with either gemcitabine 50 or 100 mg/m2. CONCLUSIONS: The concurrent use of radiotherapy and gemcitabine is effective but produces manageable severe mucositis in a high percentage of patients.     

Hyperfractionated radiotherapy and concomitant cisplatin for locally advanced laryngeal and hypopharyngeal carcinomas: final results of a single institutional program

SUMMARY: ABSTRACT The purpose of this study was to achieve locoregional control of locally advanced laryngeal carcinoma, survival, and organ preservation using split hyperfractionated accelerated radiation therapy and cisplatin concomitantly. This study was a phase II trial of chemoradiotherapy with split hyperfractionated accelerated radiation therapy, 1.6 Gy per fraction given twice per day to a total dose of 64 to 67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin 20 mg/m2, days 1 to 5, in continuous perfusion, concomitantly. Seventy-three patients were treated (stage IV, 64%). At a median follow-up of 55 months for living patients, median survival was 44 months, and 5-year overall survival and disease-free survival were 42% and 39%, respectively. Toxicities included mucositis (grade III, 40%; grade IV, 28%), epithelitis (grade III, 28%). Of the 73 patients, 32 (44%) have continued with their larynx free of disease. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin has been demonstrated to be an active treatment for locally advanced laryngeal carcinomas, but more active combinations of chemotherapy and radiotherapy, without increase of toxicity, are necessary to increase the rate of locoregional control, organ preservation, and survival.     

Three Weekly Versus Weekly Cisplatin as Radiosensitizer in Head and Neck Cancer: a Decision Dilemma

Cisplatin-based concurrent chemoradiation plays an undisputed key role as definitive treatment in unresectable patients with locally advanced squamous cell carcinoma head and neck or as an organ preservation strategy. Treatment with 100 mg/m2 3-weekly cisplatin is considered the standard of care but is often associated with several adverse events. The optimum drug schedule of administration remains to be defined and presently, there is insufficient data limiting conclusions about the relative tolerability of one regimen over the other. This review addresses regarding the optimal dose schedule of cisplatin focusing mainly on three-weekly and weekly dose of cisplatin based concurrent chemoradiotherapy in locally advanced head and neck cancer with an emphasis on mucositis, dermatitis, systemic toxicity, compliance, and treatment interruptions. To derive a definitive conclusion, large prospective randomized trials are needed directly comparing standard 3-weekly cisplatin (100 mg/m2) with weekly schedule (30 - 40 mg/m2) of concurrent cisplatin based chemoradiotherapy in locally advanced squamous cell carcinoma head and neck.     

Efficacy and Safety of Concomitant Chemoradiotherapy with Cisplatin and Docetaxel in Patients with Locally Advanced Squamous Cell Head and Neck Cancers

Background: Chemoradiation (CRT) using cisplatin-based regimens has become the standard of care in thetreatment of squamous cell head and neck cancers (SCHNC). The impact of taxanes as radiosensitizing agentswith concurrent CRT regimens is unknown. We therefore retrospectively evaluated the efficacy and tolerabilityof a weekly cisplatin+docetaxel combination with CRT in locally advanced SCHNC. Methods: Sixty-six patientswith locally advanced SCHNC (39.4% stage IV, 53% stage III, and 7.6% stage II) were assessed retrospectively.Total radiation dose to the PTV of gross disease (primary and/or node) was 70 Gy/ 35 fractions, 5 fractions perweek. Minimum doses of 60 Gy and 50 Gy were administered to PTVs of elective high risk and low risk disease,respectively. Chemotherapy (CT) consisted of weekly cisplatin (20 mg/m2)+docetaxel (20 mg/m2) concurrentlywith RT. Results: The median age of the patients was 58 years (range, 32-77). Objective response rate was 83.3%.The 2-year progression-free survival (PFS) and overall survival (OS) were 75.7% and 78.3%, respectively.The most common grade 3 and 4 toxicities were mucositis (36.4%), nausea and vomiting (12.1%), neutropenia(4.5%). Conclusion: Weekly cisplatin and docetaxel concurrent with RT for locally advanced SCHNC was foundtolerable with high efficacy.     

Concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas: radiation therapy oncology group phase II trial 99-14.

PURPOSE: To investigate the feasibility of combining concomitant boost accelerated radiation regimen (AFX-C) with cisplatin and to assess its toxicity and the relapse pattern and survival in patients with advanced head and neck carcinoma (HNC). PATIENTS AND METHODS: Between April and November of 2000, 84 patients with stage III to IV HNC who met the eligibility criteria were enrolled; 76 of these patients were analyzable. Radiation consisted of 72 Gy in 42 fractions over 6 weeks (daily for 3.5 weeks, then twice a day for 2.5 weeks). Cisplatin dose was 100 mg/m(2) on days 1 and 22. Tumor and clinical status were assessed, and acute late toxicities were graded. RESULTS: Sixty-five patients (86%) received both radiation and chemotherapy per protocol or with minor variations. The estimated 2-year locoregional relapse and distant metastasis rates were 34.7% and 16.1%, respectively. The estimated 2-year overall survival and disease-free survival rates were 71.6% and 53.5%, respectively. Three patients (4%) died of complications, 19 patients (25%) had acute grade 4 toxicity, and 49 patients (64%) had acute grade 3 toxicity. The 2-year cumulative incidence of late grade 3 to 5 toxicities was 51.3%. CONCLUSION: These data showed that it was feasible to combine AFX-C with cisplatin. The compliance to therapy was high, and the locoregional control and survival rates achieved compared favorably with AFX-C alone or other concurrent chemoradiation regimens tested by the Radiation Therapy Oncology Group. A phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin is ongoing to determine whether the use of AFX-C in the concurrent chemoradiation setting further improves outcome.     

常规放疗结合每周紫杉醇治疗局部晚期鼻咽癌Ⅱ期临床试验

[目的]探讨常规放疗结合每周紫杉醇治疗局部晚期鼻咽癌的长期疗效。[方法]局部晚期（Ⅲ～Ⅳa期）鼻咽癌患者在常规放疗的同时每周给予30mg／m。的紫杉醇化疗。[结果]38例患者,鼻咽部放疗平均剂量71．1Gy;颈部转移淋巴结放疗平均剂量60．3Gy;30例患者完成7次,7周化疗。1例因急性反应过大只完成4次化疗,还有2例和5例分别完成5次和6次化疗。未观察到明显胃肠道反应和严重血液学毒性。总有效率（CR＋PR）84．2％,中位随访时间52个月。累积1年生存率为94．7％,2年生存率86．7％,3年生存率69．9％,4年生存率58．7％．5年生存率53．1％。[结论]常规放疗结合每周紫杉醇治疗局部晚期鼻咽癌耐受性较好,疗效满意。     

An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer.

PURPOSE: The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test. RESULTS: Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77% enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P =.014) and 27% for arm C (P = not significant). CONCLUSION: The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.     

A pilot study of high-dose intraarterial cisplatin chemotherapy with concomitant accelerated radiotherapy for patients with previously untreated T4 and selected patients with T3N0-N3M0 squamous cell carcinoma of the upper aerodigestive tract

BACKGROUND: This Phase I clinical trial was developed to assess the feasibility of combining high-dose intraarterial cisplatin chemotherapy with concurrent, concomitant boost accelerated radiation therapy for patients with previously untreated T4 and select patients with T3N0-N3M0 squamous cell carcinoma of the upper aerodigestive tract. METHODS: Between July 1999, and February 2002, 19 patients were treated with 3 or 4 weekly cycles of intraarterial Cisplatin chemotherapy (150 mg/m(2)) with concurrent, concomitant boost accelerated radiation therapy (72 grays in 42 fractions over 6 weeks). RESULTS: Two patient deaths occurred among the first 15 patients enrolled. Both patients presented with febrile neutropenia, and both died of complications related to infection. The number of cycles of intraarterial cisplatin was reduced from four cycles to three cycles, and an additional four patients were treated. The fourth patient treated on the modified protocol developed febrile neutropenia, sepsis, and a thromboembolic event, which resulted in lower extremity amputations. The maximum acute toxicity experienced was Grade 2 in 6 patients, Grade 3 in 5 patients, Grade 4 in 6 patients, and Grade 5 in 2 patients. With a median follow-up of 21 months (range, 6.2-34.6 months), the overall survival at 1 year was 89.5% (95% confidence interval [95%CI], 76.7-100%). At 1 year, 92.9% of the patients were free from disease progression (95%CI, 80.3-100%). CONCLUSIONS: The results of this study suggest that concurrent intraarterial cisplatin chemotherapy at a dose of 150 mg/m(2) with concomitant boost accelerated radiation therapy is not feasible.     

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 weekly docetaxel and cisplatin concurrent with thoracic radiotherapy in Stage III non-small-cell lung cancer.

PURPOSE: This is the first report of a Phase I study on concomitant weekly cisplatin and docetaxel chemotherapy with thoracic radiation for Stage III non-small-cell lung cancer (NSCLC). The study objectives were to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of docetaxel used in this regimen, and to evaluate the feasibility of weekly concurrent chemoradiotherapy. METHODS AND MATERIALS: Patients with histologically proven and unresectable Stage III NSCLC were the subjects of this study. Cisplatin was administered at a fixed dose of 20 mg/m2, while the dose of docetaxel was increased from 0 to 30 mg/m2 in increments of 10 mg/m2. Chemotherapy was given on the first day of each week for 6 weeks. The primary tumor and regional lymph nodes were irradiated to 54 Gy, followed by an additional 9 Gy boost to the primary tumor, making the total dose 63 Gy at 1.8 Gy/fraction. RESULTS: Sixteen men and 2 women with advanced NSCLC without prior treatment were enrolled. The median age of the group was 58 years (range 49-67). Three patients had Stage IIIa disease and 15 patients had IIIb disease. Dose-limiting Grade 3 esophagitis was encountered at a docetaxel dose level of 30 mg/m2 in 2 of 3 patients. No dose-limiting, nonhematologic toxicity occurred in the other patients and no dose-limiting hematologic toxicity occurred in any patient. CONCLUSION: The treatment schedule for NSCLC was feasible, with the DLT being esophagitis. We determined the recommended dose of docetaxel to be 20 mg/m2 for a Phase II study when combined with weekly cisplatin and concomitant thoracic RT.     

紫杉醇加顺铂同步放化疗治疗局部晚期食管癌的临床研究

目的:探讨紫杉醇加顺铂(TP)同步放化疗治疗局部晚期食管癌的疗效及毒副反应。方法:48例局部晚期食管癌患者,随机分成两组,每组24例,A组为单纯放疗组,B组为每周紫杉醇加顺铂同步放化疗组。两组均采用6MV或者18MVX射线放射治疗,食管癌原发灶剂量60～68Gy,区域淋巴结剂量50～60Gy。B组放疗同时给予紫杉醇40mg/m2 DDP20mg/m2,均于d1、d8、d15、d22、d29、d36静滴。结果:单纯放疗组和紫杉醇加顺铂组的有效率(CR PR)分别为75%和88%,差异有显著性意义(P<0.05)。两组的1、3、5年局部无进展生存率分别为60.7%、21.0%和9.5%,71.2%、49.3%和19.2%,两组局部无进展生存率差异有显著性意义(P=0.034);两组的1、3、5年生存率分别为66.7%、25.0%和12.5%,79.2%、58.3%和29.2%,总生存率差异有显著性意义(P=0.041)。同步放化疗组的Ⅲ、Ⅳ级毒副反应高于单纯放疗组。结论:同步放化疗可提高局部晚期食管癌的无进展生存率和总生存率,但毒副反应有增加的趋势。     

Integrating concurrent navelbine and cisplatin to hyperfractionated radiotherapy in locally advanced non-small cell lung cancer patients treated with induction and consolidation chemotherapy: feasibility and activity results

OBJECTIVES: The purpose of this study was to determine the effectiveness and toxicity of a new combination schedule based on concurrent navelbine, cisplatin and hyperfractionated radiotherapy in patients with locally advanced NSCLC treated with platinum and gemcitabine induction and consolidation chemotherapy. MATERIALS AND METHODS: The 37 patients with pathological confirmed advanced NSCLC (non-surgical stages IIIA and IIIB) were included in the study. All of them were assessable for survival and 32 for response. The treatment schedule consisted of cisplatin (100 mg/m2) or carboplatin (400 mg/m2) on day 1 with gemcitabine (1000 mg/m2) on days 1, 8 and 15. Treatment was given every 28 days for two courses, followed by concurrent administration of accelerated modified hyperfractionated radiotherapy, with concomitant boost, with a total dose of 61.64 Gy administered for 5 weeks, with cisplatin and navelbine, for two courses, finally followed by two courses of the same initial chemotherapy. RESULTS: Four patients achieved complete response (12.5%) and 14 (44%) partial response, for an overall objective response rate of 56.5%. After a minimum follow-up duration of 35.5 months, median progression free survival was 12.2 months. The median survival was 15.4 months with actuarial 1-, 2- and 3-year survival of 67, 21 and 15%, respectively. The main toxicity was hematological. There was esophagitis (grades III and IV) in 30% of the patients and there were two treatment-related deaths. CONCLUSION: Combined treatment with concurrent radiotherapy and chemotherapy in non-surgical NSCLC is an acceptable treatment modality. However, the toxicity was not negligible.     

Lack of effectiveness of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma

BACKGROUND: Cisplatin has been reported to enhance the cell-killing effect of radiation. The current study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma. METHODS: Forty-one patients with pancreatic carcinoma that was unresectable but confined to the pancreatic region were treated with external beam radiation (50.4 grays [Gy] in 28 fractions over 5.5 weeks) and daily cisplatin (5 mg/m(2)/day as a 30-minute infusion just before each radiation fraction). Maintenance 5-fluorouracil (5-FU) (500 mg/m(2)) given once weekly was initiated 1 week after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. RESULTS: Of the 41 patients, 31 (76%) completed the scheduled course of chemoradiotherapy. The median survival time was 7.7 months, and the 1-year survival rate was 36%. The median progression free survival time was 5.8 months. The first site of failure was distant metastases in 25 patients, locoregional recurrence in 6 patients, and both sites in 1 patient. The major toxicity was leukocytopenia and nausea/emesis. CONCLUSIONS: Radiotherapy with daily cisplatin appears to be inferior to conventional chemoradiotherapy using 5-FU in patients with locally advanced pancreatic carcinoma.     

Radiochemotherapy with cisplatin and oral tegafur in advanced head and neck cancer: long-term results of a phase II study

AIMS AND BACKGROUND: To evaluate the tolerance and efficacy of an original concurrent radiochemotherapy regimen in locally advanced head and neck cancer. METHODS: Sixty-four patients with stage III or IV squamous cell carcinoma arising from a head and neck mucosal site were eligible. Simultaneous radiochemotherapy consisted of two courses of continuous infusional cisplatin (20 mg/m2/d, days 1-4 and 29-32) and oral tegafur (1200 mg/d, days 1-14 and 29-43), together with conventional radiation therapy up to a total dose of 70-75 Gy over nine weeks. RESULTS: All the patients were evaluated for toxicity and response. Acute mucositis was the most prevalent complication. Grade 3 toxicities were mucositis (44%), skin toxicity (10%), leukopenia (8%), and thrombocytopenia (1%). No toxic death was observed. Complete response to treatment was observed in 72% of patients. With a median follow-up of 48.5 months (range, 27-84), 5-year actuarial rate of local-regional control, disease-free survival, overall survival and disease-specific survival were 60% (95% confidence interval [CI], 40-70%), 55% (95% CI, 45-65%), 51% (95% CI, 43-59%) and 61% (95% CI, 53-69%), respectively. CONCLUSIONS: Response, local-regional control and survival rates are equivalent to those reported from other concomitant radiochemotherapy combinations. However, the regimen offers the advantage of its tolerance and toxicity profile.     

Concomitant boost radiation and concurrent cisplatin for advanced head and neck carcinomas. Preliminary results of a phase II, single-institutional trial

INTRODUCTION: This study aims to asses the effectiveness and toxicity of boost radiotherapy concomitant and concurrent cisplatin for patients with locally advanced head and neck cancer (LAHNC). MATERIAL AND METHODS: There were 30 patients included in a prospective, phase II single-institution trial and of whom, 29 were at AJCC stage IV and 1 at stage III. Treatment consisted of radiotherapy acceleration fractionation with concomitant boost, 72 Gy, and 2 cycles of concomitant cisplatin (20 mg/m2/day continuous infusion; days 1-5 and 29-33). Amifostine, (i.v. 200 mg/m2) was administered to 26 prior to the first fraction of radiotherapy. Endpoints of the study were quality-of-life (QL), overall survival, and local control of disease. RESULTS: Complete response (CR) was achieved in 23 patients (77%), 2 patients had partial response (PR) (7%), 4 had no response (13%), and 1 was not evaluated for response. The 2-year overall survival and loco-regional control were 60% and 56%, respectively. Main toxicity was grade 3 or 4 mucositis in 93% of the patients. QL scores (questionnaire QLQC30; version 3.0) and the HN cancer module QLQ-HN35) showed a worsening in areas related to the treatment e.g. dry mouth, problems stretching the mouth, and sticky saliva. CONCLUSIONS: this combination modality is active, but toxic, in the treatment for LAHNC. Concomitant boost radiotherapy is probably, not the best radiotherapy schema for combining with chemotherapy in LAHNC.     

Phase II trial: concurrent radio-chemotherapy with weekly docetaxel for advanced squamous cell carcinoma of head and neck

Abstract Introduction: Standard fractionation radiation therapy (RT) combined with concomitant chemotherapy (CT) based on cisplatin schemes is actually the standard treatment for locally advanced non-resectable squamous cell carcinoma of head and neck (SCCHN). The appearance of taxoids has introduced a new kind of treatment with high antitumoral power. The aim of this study is to add more information about the role of this new approach. Materials and methods: Twenty-six patients with locally advanced non-resectable SCCHN were recruited at six institutions in Spain, between January 2001 and January 2003. Docetaxel was administered weekly, for 6 weeks, concurrently with RT. Results: The mean total delivered dose of RT was 70’2 Gy (range 64-74 Gy). The median and mean duration of time were 63 days and 61 days (range 49-103 days) respectively. After a median time control of 19 months (range 3.3-42.2 months), the response rate was 83.4%. The median time to local progression was 16.4 months (95% confidence interval [CI]=4.4-28.4 months). The median survival time was 26.9 months, with one- and two-year overall survival of 66.9% (95% CI=48.1-85.7%) and 57.5% (95% CI=37.3-77.7%) respectively. The median duration time response was 15.1 months (95% CI=3.7-26.5 months). The median time until treatment failure was 9.4 months (95% CI=4.7-14.1). Incidence of grade III-IV mucositis was 88%, neutropenia 72% and skin toxicity 92% (24% grade III-IV). The incidence of severe late toxicity (grade III and IV) due to RT/CT was 31.4%. Conclusions: Although therapeutics results are equivalent to cisplatin schemes of concurrent CT-RT, mucositis and cutaneous toxicity registered in this trial must be considered as limiting factors to application of this new approach.     

Concurrent Chemoradiotherapy for Salvage in Relapsed Squamous Cell Head and Neck Cancer

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m²/day and cisplatin 20 mg/m²/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locore-gional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.