Paclitaxel and carboplatin concurrent with radiotherapy for primary cervical cancer

BACKGROUND: Concurrent radiochemotherapy is currently considered the new standard treatment in locally advanced cervical cancer. PATIENTS AND METHODS: Eight women with cervical cancer stage IB2-IVA were treated with standard radiation therapy in combination with standard carboplatin (AUC=2, once weekly, x 6) and escalating doses of paclitaxel (60 mg/m2, once weekly, x 4, then x 5 and x 6). RESULTS: At the lowest dose level, four weekly paclitaxel cycles in six patients, three developed grade III diarrhoea and one severe radiation enteritis several weeks after radiotherapy. Two patients did not achieve complete remission and underwent additive salvage hysterectomy. All patients remained free of local recurrence, but one patient had distant metastases after 13 months. The median disease-free survival was 25 months with a median follow-up of 26 months. CONCLUSION: Standard pelvic radiotherapy in combination with weekly carboplatin and paclitaxel is poorly tolerated due to dose-limiting diarrhoea.     

Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement

BACKGROUND AND PURPOSE: Post-operative radiotherapy is indicated for the treatment of head and neck cancers. In vitro, chemotherapy potentiates the cytotoxic effects of radiation. We report the results of a randomized trial testing post-operative radiotherapy alone versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. MATERIALS AND METHODS: The study involved patients undergoing curative-intent surgery for head and neck cancers with histological evidence of lymph node involvement. Patients were randomly assigned to receive radiotherapy alone (54-72Gy, 30-40 fractions, 6-8 weeks) or identical treatment plus concomitant Carboplatin (50mg/m(2) administered by IV infusion twice weekly). RESULTS: Between February 1994 and June 2002, 144 patients were included. With a median follow-up of 106 months (95% confidence interval (CI) [92-119]), the 2-year rate of loco-regional control was 73% (95% CI: 0.61-0.84) in the combined treatment group and 68% (95% CI: 0.57-0.80) in the radiotherapy group (p=0.26). Overall survival did not differ significantly between groups (hazard ratio for death, 1.05; 95% CI: 0.69-1.60; p=0.81). CONCLUSIONS: Twice-weekly administration of carboplatin concomitant to post-operative radiotherapy did not improve local control or overall survival rates in this population of patients with node-positive head and neck cancers.     

含紫杉醇化疗方案治疗晚期头颈部恶性肿瘤

目的：探讨紫杉醇类药物分3周疗法治疗晚期头颈部恶性肿瘤的价值和毒性。方法：对51例临床Ⅲ-Ⅳ期的头颈部恶性肿瘤患者（初治19例,复治32例）选用紫杉醇与卡铂或顺铂联合治疗：紫杉醇75－100mg/m^2,静滴,第1、8、15天,卡铂300－350mg/m^2,静滴,第2天,(或顺铂20mg/m^2,静滴,第1－5天）。每4周重复,共展3－6周。结果：51例患者完全缓解（CR）4例（7．8％）,部分缓解（PR）15例（29．4％）,无变化（NC)18例（35．3％）,进展（PD）14例（27．4％）,总有效率（RR）37．2％。疗程中出现耐药复发或转移的11例（21．6％）。其中初治的19例患者中,CR2例（10．50）,PR6例（31．6％）,RR为42．1％,较复治患者的RR有显著性差异（P＜0．05）。主要不良反应：骨髓抑制、肢体感觉异常、面色潮红、发热、脱发、消化道反应,并出现可疑过敏性休克死亡1例（2．0％）。结论：含紫杉醇的化疗方案治疗晚期头颈部恶性肿瘤有较好的疗效,即使在治疗对常规化疗耐药的患者也能取得一定的疗效,多数毒副作用处于可以耐受范围,但可能有严重的过敏性反应。     

Paclitaxel and carboplatin in neo-adjuvant and concomitant chemoradiotherapy in locally advanced head and neck squamous cell carcinoma

AIM AND BACKGROUND: To evaluate feasibility of neoadjuvant chemotherapy (NA-CT) followed by CT + radiotherapy (RT) in locally advanced or unresectable head and neck squamous cell carcinoma (HNSCC). METHODS: 22 HNSCC patients were enrolled (18 males, 4 females; median age, 59.5 years; median ECOG PS, 1). Sites of disease: oral cavity, 18.2%; oropharynx, 40.9%; hypopharynx, 18.2%; larynx, 4.6%, multiple sites, 18.2%. T (tumor) category: T2, 13.6%; T3, 31.8%; T4, 54.5%. N (nodes) category: NO, 9.1%; N1, 18.1%; N2, 40.9%; N3, 31.8%. Stage: III, 4.6%; IVA, 63.6%; IVB, 31.8%. Induction carboplatin (AUC = 6) and paclitaxel (200 mg/m2) x 3 cycles (q21 days) were given. Responders received definitive radiotherapy with concurrent carboplatin (35 mg/m2/day from days 1 to 5 in weeks 1, 3, 5 and 7) and paclitaxel (50 mg/m2 on days 10, 24 and 38). Patients with node involvement were suggested to undergo postradiotherapy neck dissection. RESULTS: NA-CT. 97% of planned chemotherapy cycles were administered. Prevalent toxicity was hematologic: 50% G4 neutropenia and 31.8% G3, one neutropenic fever. All patients had alopecia. Complete responses in T and N were 4 (18.2%) and 3 (15%), respectively. Partial responses were 13(59%) and 9 (45%). There was 1 progressive disease. CT + RT. 79.9% of planned cycles of CT were administered. In 19 patients (86.4%) more than 50% of planned cycles of CT were completed. Median dose of RT was 70.2 Gy on T/N+ and 54 Gy on NO. Limiting toxicity was mucositis in 77.3%, followed by neutropenia (59.1% G3-G4). Median weight loss was 4.9%.18.2% of patients required hospitalization. Complete responses in T and N were 15 (68.1%) and 8 (40%), respectively. Partial responses were 5 (22.7%) and 7 (35%). CONCLUSIONS: The preliminary results of this study are encouraging, despite the toxicity. Adequate follow-up is required to evaluate efficacy in terms of local-regional control and overall survival.     

Accelerated postoperative radiotherapy with weekly concomitant boost in patients with locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: To assess the feasibility and efficacy of accelerated 66-Gy postoperative radiotherapy (PORT) using a single-fraction regimen from Mondays to Thursdays and a concomitant boost on Friday afternoon sessions in patients with locally advanced head and neck cancer (LAHNC). PATIENTS AND METHODS: Between December 1997 and June 2002, 89 consecutive patients with pT1-pT4 and/or pN0-pN3 LAHNC were included. PORT was indicated in patients with positive surgical margins, T4 tumors, or extracapsular nodal infiltration. RT consisted of 66 Gy (2 Gy/fr) in 5 weeks and 3 days. Median follow-up was 21 months (range 2-59). RESULTS: Acute morbidity was acceptable: grade 3 mucositis in 20 (22%) patients, grade 3 dysphagia in 22 (25%) patients, and grade 3 skin erythema in 18 (20%) patients. Median weight loss was 2 kg (range 0-14.5). No grade 4 toxicity was observed. Late effects included grade 3 xerostomia in 6 (7%) patients, and grade 3 edema in 2 (2%) patients. Median time to locoregional relapse was 10 months (range 2-21). Two-year overall, cause-specific, and disease-free survival rates were 70% (95% confidence interval (CI) 59-81), 75% (95% CI 64-86), and 63% (95% CI 52-74), respectively. The 2-year actuarial locoregional control rate was 80% (95% CI 70-90). Distant metastasis probability at 4 years was 38% (95% CI 20-56). Multivariate analysis revealed that pT-classification (pT1-2 vs. pT3-4) and extranodal extension (0, 1 vs. 2 or more) were the two factors independently influencing the outcome. CONCLUSIONS: We conclude that reducing the overall treatment time using an accelerated PORT schedule including a once-weekly concomitant boost (six fractions per week) is easily feasible with excellent local control. Acute and late RT-related morbidity is acceptable. Given the disease progression pattern (distant metastases), adjuvant chemotherapy should be considered.     

Radiotherapy with concomitant chemotherapy for head and neck cancer

Concomitant chemoradiotherapy has already resulted in statistically significantly improved disease-free and overall survival for patients with head and neck cancer. Although the differences observed so far have been small, it is of note that the improved outcome was achieved even though only single-agent chemotherapy was used. More recent, chemoradiotherapy schedules have employed more aggressive chemotherapy regimens, frequently with split-course radiotherapy. Several of these schedules have resulted in encouraging response and survival figures in phase II trials. At the same time, toxicities, usually in the form of mucositis, have also been increased. The role of these schedules in the management of patients with advanced head and neck cancer will need further evaluation, eventually using a randomized format comparing such a regimen with standard radiotherapy alone. Their use outside of clinical trials cannot be recommended yet.     

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk,resected head and neck cancer

Addition of panitumumab to adjuvant chemoradiation is tolerable and provides promising clinical acivity for high risk, resected head and neck squamous cell carcinoma.BackgroundTreatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC.Patients and methodsEligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60–66 Gy over 6–7 weeks) concurrent with weekly cisplatin 30 mg/m² and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS).ResultsForty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12–90 months). The probability of 2-year PFS was 70% (95% CI = 58%–85%), and the probability of 2-year OS was 72% (95% CI = 60%–87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%).ConclusionsIntensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted.Registered clinical trial numberNCT00798655     

Modern radiotherapy for head and neck cancer

Radiation therapy (RT) plays a key role in curative-intent treatments for head and neck cancers. Its use is indicated as a sole therapy in early stage tumors or in combination with surgery or concurrent chemotherapy in advanced stages. Recent technologic advances have resulted in both improved oncologic results and expansion of the indications for RT in clinical practice. Despite this, RT administered to the head and neck region is still burdened by a high rate of acute and late side effects. Moreover, about 50% of patients with high-risk disease experience loco-regional recurrence within 3 years of follow-up. Therefore, in recent decades, efforts have been dedicated to optimize the cost/benefit ratio of RT in this subset of patients. The aim of the present review was to highlight modern concepts of RT for head and neck cancers considering both the technological advances that have been achieved and recent knowledge that has informed the biological interaction between radiation and both tumor and healthy tissues.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.     

头颈部肿瘤放疗对甲状腺功能的损伤

头颈部肿瘤放疗后会引起不同程度的甲状腺功能减退.引起甲状腺功能减退的机制包括射线对甲状腺及垂体细胞的直接损伤、对相关血管的损伤以及自身免疫反应等.影响头颈部肿瘤放疗后甲状腺功能的因素主要有:放疗剂量、放疗技术、是否联合手术化疗等.通过对这些影响因素的研究可为防治甲状腺功能减退提供依据,从而提高患者生活质量.