Pilot study of organ preservation multimodality therapy for locally advanced resectable oropharyngeal carcinoma

The purpose of this study was to determine the early efficacy and toxicity of a new multimodality organ-preservation regimen for locally advanced, resectable oropharyngeal squamous cell carcinoma (SCC). Patients with T3-4N0-3M0 or T2N2-3M0 oropharyngeal SCC were eligible for this Phase II study. Patients needed the physiologic reserve for surgery and technically resectable tumors. Induction carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) x 2 cycles (q21 days) were given. Objective responders received definitive radiotherapy (XRT), 70 Gy/7 weeks with concurrent weekly paclitaxel. Initially, the dose of paclitaxel was 50 mg/m2/week; because of mucosal toxicity it was reduced to 30 mg/m2/week. Patients with N2-3 disease received post-XRT neck dissection and 2 more cycles of "adjuvant" chemotherapy. In the first 22 patients, the neutropenic fever rate was 27%. Although there has been no grade IV-V toxicity from induction therapy, grade II-III toxicity resulted in an unacceptable delay in starting XRT in 14% of patients. The response rate to induction chemotherapy was 91%. Grade III mucositis occurred in all patients during concurrent chemoradiotherapy. One patient died of pneumonia during concurrent chemoradiotherapy after receiving 26 Gy and 3 doses of paclitaxel 50 mg/m2. No dose-limiting toxicity occurred in 15 patients treated with concurrent paclitaxel 30 mg/m2/week. Actuarial overall survival at 18 months is 82%; local-regional control is 86%. To date, distant metastases have not developed in any patients. This regimen has intense but acceptable acute toxicity. The maximum tolerated dosage of weekly paclitaxel during standard continuous-course XRT is confirmed to be 30 mg/m2/week. The treatment efficacy of this regimen (response rate and short-term local-regional and distant control) is encouraging. Accrual continues to obtain long-term toxicity, efficacy, and quality-of-life data.     

Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation

The use of induction chemotherapy prior to chemoradiation for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains controversial. We explored whether toxicity from induction chemotherapy influenced the delivery of concurrent chemoradiation. Among 171 consecutive previously unirradiated patients with HNSCC treated with combined chemotherapy and radiation, we identified 66 patients with stage III-IVB head and neck carcinoma who were treated with induction chemotherapy prior to planned chemoradiation. The most common induction regimen was docetaxel, cisplatin and 5-FU (TPF; 80%) for 2 to 3 cycles. Mean radiation dose was 72 Gy (range, 36-75 Gy). Concurrent chemotherapy regimens included cisplatin (26%), cetuximab (5%) and 5-fluorouracil/hydroxyurea (65%)-based regimens. At a median follow-up of 27 months (range, 9-56 months), the 2-year locoregional control and distant control rates were 85 and 86%, respectively. The 2-year disease-free survival and overall survival rates were 74 and 80%, respectively. Although there were no grade 5 toxicities during induction chemotherapy, 26% of patients required hospitalization for adverse events, including 5% needing intensive care. The most common high grade adverse events were grade 4 neutropenia (21%) and neutropenic fever (17%). Six percent of patients were unable to tolerate concurrent chemotherapy. The 2-year disease-free survival was significantly higher in patients able to complete induction and concurrent chemoradiation as planned (83 vs. 27%, p<0.001). Induction chemotherapy followed by concurrent chemoradiation results in promising survival rates in our cohort of advanced head and neck carcinoma patients. Due to severe toxicities in a subset of patients, this strategy is only recommended in selected high-risk patients who are carefully followed by an experienced multidisciplinary team.     

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。     

Paclitaxel, carboplatin, and gemcitabine in the treatment of patients with advanced transitional cell carcinoma of the urothelium

BACKGROUND: The objective of the current study was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, carboplatin, and gemcitabine in patients with advanced urothelial carcinoma. METHODS: Patients with metastatic or locally unresectable transitional cell carcinoma of the urothelium who had received either no or one previous systemic chemotherapy regimen were eligible. All patients received chemotherapy with intravenous paclitaxel at a dose of 200 mg/m(2) on Day 1, intravenous carboplatin at an area under the serum concentration-time curve of 5.0 on Day 1, and intravenous gemcitabine at a dose of 1000 mg/m(2) on Days 1 and 8. Treatment courses were repeated every 21 days. Patients were evaluated for response after they completed two treatment courses; patients who achieved an objective response and stable disease continued treatment for a total of six courses or until tumor progression. RESULTS: Sixty patients were treated between January 2000 and September 2003. Thirty-five patients (58%) had > or = 1 visceral sites of metastases, and only 4 patients (7%) had received any previous systemic chemotherapy. Twenty-six patients (43%) had achieved objective responses to treatment (12% complete responses). The median actuarial survival was 11 months, and the actuarial 1-year and 2-year survival rates were 46% and 27%, respectively. Myelosuppression was the most frequent toxicity, and Grade 3-4 neutropenia (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) occurred in 72% of patients (46% of courses). Ten patients were hospitalized for the treatment of neutropenia and fever, and 1 patient died of treatment-related causes. Nonhematologic toxicities were relatively uncommon. CONCLUSIONS: The combination of paclitaxel, carboplatin, and gemcitabine was an active and tolerable regimen for patients with advanced urothelial carcinoma. However, the regimen was more toxic and showed no obvious incremental increase in efficacy compared retrospectively with various two-drug regimens.     

Radiotherapy and concurrent low-dose paclitaxel in locally advanced head and neck cancer.

In our prospective study we examined the use of low-dose paclitaxel concurrently with radiation for patients with locally advanced head and neck cancer, who were not eligible for concurrent chemoradiation due to their poor general condition. Twenty-six patients were treated with external beam radiotherapy and received concomitantly 2 mg/m(2) paclitaxel three times a week. Beside an acceptable efficacy (RR: 65%, 2-year overall survival 46%) the treatment was well tolerated and resulted in a favorable toxicity profile. This regimen is resource effective and allowed successive therapy if it was necessary and therefore may serve as an alternative for patients in poor condition with locally advanced head and neck cancer.     

紫杉醇卡铂周方案同步化疗联合三维适形放射治疗局部晚期非小细胞肺癌的临床研究

目的观察紫杉醇卡铂周方案同步化疗联合三维适形放疗(3D-CRT)治疗局部晚期非小细胞肺癌(NSCLC)的毒性反应及疗效。方法采用前瞻性非随机对照方法,将52例局部晚期NSCLC患者分为同步组(21例):采用紫杉醇和卡铂周方案化疗联合同步3D-CRT;序贯组(31例):采用紫杉醇和卡铂序贯化疗联合3D-CRT。同步组紫杉醇40 mg/m2,静脉滴注1h;卡铂AUC 1.5。序贯组在放疗前行2周期的紫杉醇和卡铂辅助化疗,紫杉醇150 mg/m2,第1天、第21天;卡铂AUC 5,第1天、第21天。3D-CRT 1.8～2.0 Gy/d,总剂量60～66 Gy/6～8周。结果52例患者全部完成治疗。有12例患者在治疗过程中由于白细胞减少而导致治疗时间延长1周以上,其中同步组5例,序贯组7例。同步组中,肺原发灶完全缓解(CR)为9.5%(2/21),部分缓解(PR)为71.4%(15/21),无变化和进展(NC PD)为19.0%(4/21),有效率(CR PR)为81.0%。序贯组中,肺原发灶CR为6.5%(2/31),PR为67.7%(21/31),NC PD为25.8%(8/31),CR PR为74.2%。同步组和序贯组患者的Ⅱ～Ⅲ级急性放射性食管炎、Ⅱ～Ⅲ级急性放射性肺炎和Ⅱ～Ⅲ级白细胞减少发生率分别为61.9%(13/21)和41.9%(13/31)、23.8%(5/21)和22.6%(7/31)及42.9%(9/21)和19.4%(6/31)。同步组有1例患者出现Ⅳ级白细胞减少。52例患者的中位生存时间为17.5个月(同步组19.0个月,序贯组15.8个月),1、2年总生存率分别为72.0%和37.0%,1、2年局部控制率分别为75.0%和75.0%。结论同步放化疗是一种安全有效的治疗方法,绝大多数患者能耐受治疗。同步组与序贯组相比,有提高有效率和延长生存率的趋势,但差异并无统计学意义。     

Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer

PURPOSE: Neck dissection has traditionally played an important role in the treatment of patients with squamous cell carcinoma of the head and neck who present with regionally advanced neck disease (N2-N3). Radiotherapy and concurrent chemotherapy improves overall survival in advanced head-and-neck cancer compared with radiotherapy alone. The necessity for postchemoradiation neck dissection is controversial. The intent of this report was to define the value of neck dissection in this patient population better. METHODS AND MATERIALS: Patients with locally advanced squamous carcinoma of the head and neck who also presented with nodal disease and underwent hyperfractionated radiotherapy and concurrent cisplatin/5-fluorouracil chemotherapy constituted the study population. Adjuvant modified neck dissection (MND) was planned 6 to 8 weeks after completion of chemoradiation in those patients who had a biopsy-proven pathologically complete response at the primary tumor site, irrespective of the clinical/radiographic neck response. A cohort of patients underwent electrode assessment of tumor oxygenation. Pathologic findings from the MND were used to compute the negative and positive predictive values and overall accuracy of the clinical/radiographic response (cCR). Regional control, failure-free survival, and survival were compared according to whether patients actually underwent MND. RESULTS: A total of 154 patients received concurrent chemoradiation. Of these, 108 presented with nodal disease: N1, n = 30; and N2-N3, n = 78. MND was performed in 65 (60%) of 108 patients, including 13 (43%) of 30 with Stage N1 and 52 (66%) of 78 with Stage N2-N3. For N1 patients, the negative predictive value of a cCR, positive predictive value of less than a cCR, and the overall accuracy for clinical response was 92%, 100%, and 92%, respectively. For N2-N3 patients, the corresponding values were 74%, 44%, and 60%. Patients with poorly oxygenated tumors were more likely to have residual disease at MND. The median follow-up was 4 years. The 4-year disease-free survival rate was 70% for N1 patients, irrespective of the clinical response or whether MND was performed. The 4-year disease-free survival rate was 75% for N2-N3 patients who had a cCR and underwent MND vs. 53% for patients who had a cCR but did not undergo MND (p = 0.08). The 4-year overall survival rate was 77% vs. 50% for these two groups of patients (p = 0.04). CONCLUSION: The clinical and pathologic responses in the neck correlated poorly with one another for patients with N2-N3 neck disease undergoing concurrent chemoradiation for advanced head-and-neck cancer. MND still appears to confer a disease-free survival and overall survival advantage with acceptably low morbidity. Tumor oxygenation assessment may be useful in selecting patients who are especially prone to have residual disease. Better tools need to be developed to determine prospectively whether this procedure is required for individual patients.     

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.     

Comparison of outcomes for patients with unresectable, locally advanced non-small-cell lung cancer treated with induction chemotherapy followed by concurrent chemoradiation vs. concurrent chemoradiation alone

PURPOSE: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. METHODS AND MATERIALS: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. RESULTS: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p = 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40-0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p = 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28-0.78; p = 0.003). CONCLUSION: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung.     

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。     

时辰诱导化疗序贯同步放化疗治疗局部晚期头颈部鳞癌的临床疗效观察

目的：观察时辰诱导化疗序贯同步放化疗治疗局部晚期头颈部鳞癌的近期疗效、毒副反应。方法：对50例不可切除的局部晚期头颈部鳞癌先给予2-3周期 TPF 时辰诱导化疗,多西他赛75mg/m2,顺铂75mg/m2,分5天完成,静滴给药,每天10：00-22：00;5-氟尿嘧啶750mg/（m2·d）,第1-5天,持续静滴,每天22：00-10：00,21天为1周期,然后调强放疗（ IMRT）,顺铂80mg/m2,3周重复同期化疗,治疗结束后评价疗效及毒副反应,并统计2年生存率。结果：50例均可评价疗效,其中CR 19例,PR 12例,SD 11例,PD 8例,总有效率（ CR﹢PR）62.0％,疾病控制率（ CR﹢PR﹢SD）84.0％。2年总生存率58.0％。结论：时辰诱导化疗后序贯同步放化疗治疗局部晚期头颈部鳞癌临床疗效较好,毒副反应可耐受。     

Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck

BACKGROUND: The objective of this study was to determine prognostic factors for response and survival on three consecutive institutional trials utilizing concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck (SCCHN). METHODS: Since 1985, patients with locally advanced SCCHN at the University of Maryland have been managed with concurrent chemotherapy and radiation therapy (RT). Three consecutive pilot studies have been performed evaluating the utility of weekly chemotherapy with standard fractionated RT. Chemotherapy consisted of carboplatin either alone (28 patients) or in combination with bleomycin (23 patients) or paclitaxel (60 patients). In all three studies, RT was given to 70.2 gray (Gy) at 1.8 Gy/fraction/day to the primary site. All patients had locally advanced SCCHN and were believed to be poor surgical candidates. Sixty-seven percent of patients had T4 disease, and 21% had T3 disease. Seventy-five percent of patients had N2-N3 disease. One hundred eleven patients were examinable for toxicity, response, and survival analysis. Factors including age, race, gender, primary site location, histologic grade, T classification, N classification, and treatment regimen were evaluated to identify predictors of these endpoints. RESULTS: The median follow-up for patients treated on study 1 (carboplatin and RT) and study 2 (carboplatin and bleomycin [C + B]/RT) was 98 months, and it was 30 months for study 3 (carboplatin and paclitaxel [C + P]/RT). The complete response rates were 54%, 52%, and 70% respectively (P = 0.01). Multivariate analysis identified length of treatment break (< 1 week vs. > 1 week) as the only predictor of complete response to therapy. The local control for the entire group was 50%. The local control for C + P/RT was 63%, versus 32% and 36% for C/RT and C + B/RT respectively (P = 0.004). The 2-, 3-, and 5-year disease free and overall survivals for the entire population were 41%, 41%, and 35% and 42%, 36%, and 33%, respectively. The 3-year overall survival rates by treatment regimen were 18% (C/RT), 35% (C + B/RT), and 47% (C + P/RT; P = 0.01). On univariate analysis, age younger than 50 years (P = 0.01), treatment with C + P/RT (P = 0.005), and treatment break of 5 days or fewer (P < 0.05) were also predictive of improved overall survival. On multivariate analysis, only complete response (P < 0.0001) and treatment with C + P/RT (P = 0.02) remained statistically significant. CONCLUSIONS: Chemoradiation provides patients with locally advanced SCCHN the opportunity for long term survival. Among the three chemoradiation regimens studied, C + P/RT was associated with the best complete response and survival rates. Complete response to therapy was the single most important predictor of overall survival. These three consecutive concurrent chemotherapy and radiation trials achieved a 5-year survival of greater than 30% for the entire population. These results support the use of this nonoperative approach for this group of patients with a historically poor prognosis.     

紫杉醇联合铂类与放疗同步治疗局部晚期食管癌的临床研究

目的探讨常规剂量紫杉醇联合铂类与放疗同步治疗食管癌的疗效,以及扩大照射野对同步放化疗疗效的影响。方法89例局部晚期食管癌初治患者,采用根治性同步放化疗,扩大野组51例,常规野组38例。放疗总剂量60 Gy(分两阶段进行),放疗的第1周和第4周给予常规剂量的紫杉醇和铂类化疗。结果87.6%的患者完成了治疗计划,扩大野组和常规野组的治疗有效率分别为75.5%和66.7%(P=0.37)。两组的Ⅲ级以上急性毒副反应主要为白细胞、血小板下降和放射性食管炎,主要远期放射损伤为肺纤维化,两组间各种毒副反应发生率差异均无统计学意义。患者总的3年生存率为32.8%,3年无复发转移生存率为34.5%,3年局部控制率为44.0%;扩大野组和常规野组的3年生存率、3年无复发转移生存率、3年局部控制率之间差异均无统计学意义。完成治疗计划的Ⅱ、Ⅲ期患者中,扩大野组3年生存率、3年无复发转移生存率及3年局部控制率较常规野组显著提高。结论常规剂量紫杉醇联合铂类化疗同步扩大野放疗对食管癌患者是安全的,可增加Ⅱ、Ⅲ期食管癌患者的局部控制率,提高3年生存率。     

局部晚期鼻咽癌放疗同步ＰＦ方案或顺铂单药的临床对照研究

目的　对比观察顺铂（ＤＤＰ）单药用于局部晚期鼻咽癌同步放化疗与ＤＤＰ联合氟尿嘧啶（５-ＦＵ）方案（ＰＦ方案）同步放化疗的有效性和安全性。方法　７６例局部晚期鼻咽癌分为两组,４０例接受ＰＦ方案同步放化疗（５-ＦＵ５００ｍｇ／ｍ^２静滴,ｄ１～ｄ５;ＤＤＰ８０ｍｇ／ｍ^２静滴,ｄ１,２１天为１周期）,３６例接受ＤＤＰ单药同步放化疗（ＤＤＰ４０ｍｇ／ｍ２静滴,每周１次,共７次）。鼻咽部病灶及颈部阳性淋巴结给予放疗总量为７０Ｇｙ,颈部预防性照射给予放疗量５０Ｇｙ。结果　全部患者均可评价疗效和毒副反应,ＰＦ方案组及ＤＤＰ单药组有效率均为１００％。ＰＦ方案组的１、３年生存率分别为１００％、８５％,ＤＤＰ单药组分别为１００％、８９％（Ｐ＞０.０５）;ＰＦ方案组与ＤＤＰ单药组的３年无进展生存率分别为７７.５％和７５.０％ （Ｐ＞０.０５）;ＰＦ方案组的中位生存时间为５０.６个月,ＤＤＰ单药组为４８.０个月（Ｐ＞０.０５）。两组毒副反应以恶心呕吐、口腔黏膜炎及白细胞减少为主,差异均有统计学意义（Ｐ＜０.０５）。结论　ＤＤＰ单药与ＰＦ方案用于局部晚期鼻咽癌同步放化疗的疗效相近,患者均可耐受,但ＤＤＰ单药组反应较轻。     

Long-term outcomes with concurrent carboplatin, paclitaxel and radiation therapy for locally advanced, inoperable head and neck cancer.

BACKGROUND: Our goal was to evaluate long-term efficacy outcomes of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with carboplatin, paclitaxel (Taxol) and radiotherapy. PATIENTS AND METHODS: We conducted a phase II trial in inoperable patients with locally advanced SCCHN. Carboplatin 100 mg/m(2) and paclitaxel 40 mg/m(2) were administered i.v. once a week during external beam radiation therapy (180 cGy per fraction) for 6-7 weeks. Interstitial brachytherapy was used as a boost in selected patients with primary malignancies of the oral cavity and the oropharynx. RESULTS: Fifty-five patients were enrolled. Fifty-two patients (95%) had stage IV and 51 (93%) had technically unresectable disease; 62% had an oropharyngeal primary site. Twenty-one patients underwent brachytherapy boost. Grade 3 or 4 mucositis occurred in 30% of patients. One death occurred during treatment that was related to complications of gastrostomy tube placement. Forty of 50 assessable patients (80%) had an objective response, with a complete response rate of 52%. With a median follow-up of 69 months for surviving patients, the 5-year progression-free survival was 36% and the 5-year overall survival was 35%. Two of the 18 long-term survivors of >50 months were gastrostomy tube feeding dependent. Patients undergoing brachytherapy boost (n = 21) had similar outcomes compared with the rest of the patients. In multivariate analysis, baseline hemoglobin levels and N stage were predictive of survival. CONCLUSION: Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.     

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy. Patients whose disease remained unresectable after initial therapy received further RT with concurrent paclitaxel/carboplatin. Of 107 patients entered into this clinical trial, only 20 patients (19%) were considered to have surgically resectable disease at the time of study entry. Ninety-eight patients (92%) completed preoperative combined-modality therapy. Forty-nine patients (46%) underwent thoracotomy and 34 patients had definitive resection. Fourteen patients (13%) had pathologic complete response (pCR). Thirteen of 18 patients (72%) with clinical stage T3 N0 (IIB) tumors had definitive resections, and 33% had pCR. After a median follow-up of 32 months, the 1- and 2-year actuarial survival rates for the entire group are 64% and 42%, respectively. Favorable-prognosis subgroups included patients who had definitive resection and patients with clinical stage T3 N0 tumors (2-year survival rates of 67% for both subgroups). Preoperative therapy with RT and weekly paclitaxel/carboplatin showed activity in this patient population; however, disease in the majority of patients with extensive involvement of mediastinal nodes remained unresectable after this treatment. Results in patients who initially had unresectable disease do not appear different than results achieved with concurrent RT/chemotherapy approaches. Postoperative complications associated with this preoperative combined-modality regimen were more frequent than expected with resection alone.     

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study)

PURPOSE: We conducted a prospective phase II study to determine the response rate, toxicity, and survival rate of concurrent weekly paclitaxel, carboplatin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC). The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. METHODS AND MATERIALS: Forty-three patients with unresectable stage IIIA and IIIB NSCLC from the Vanderbilt Cancer Center and Affiliate Network (VCCAN) institutions were entered onto the study from June 1996 until May 1997. Weekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplatin (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) were delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). RESULTS: Forty-two patients were evaluable for response and toxicities. Three patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. (66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rates of all 43 patients were 61.6% and 35% respectively, with a median survival time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (26%). There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary toxicities. CONCLUSIONS: Weekly paclitaxel, carboplatin, plus concurrent hyperfractionated RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more toxic chemoradiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/carboplatin/HFX RT in a phase III study.     

Induction chemotherapy with paclitaxel and cisplatin, followed by concomitant cisplatin and radiotherapy for the treatment of locally advanced nasopharyngeal carcinoma

PURPOSE: To evaluate the efficacy and outcome of neoadjuvant paclitaxel and cisplatin chemotherapy followed by concurrent cisplatin and irradiation in patients with locally advanced nasopharyngeal (NP) squamous cell carcinoma. PATIENTS AND METHODS: The trial included 36 patients with locally advanced nasopharyngeal squamous carcinoma presented to Radiation Oncology and Otolaryngology departments-Ain Shams university hospitals, and Sohag Cancer Center between November 2002 and March 2006. Eligible patients were treated first with three cycles of induction chemotherapy (IC), paclitaxel (175 mg/m2 on day 1) and cisplatin (80 mg/m2 on day 1) followed by concomitant conventionally fractionated radiation (70 Gy in 2 Gy fractions) and cisplatin 20-mg/m2/day on days 1- 5, 22-26 and 43-47 of the radiation therapy. RESULTS: Twenty nine patients (80%) and 32 patients (89%) achieved objective response after IC and concomitant chemoradiation (CCRT) respectively. The actuarial 3 years survival was 68%, and the actuarial 3 year progression free survival (PFS) was 66%. Survival and PFS were significantly better for patients with smaller tumor volume (stage III), compared with patients with stage IV. Thirteen patients (36%) have elements of local and/or regional failure and 5 patients (14%) have an element of distant metastasis. Neutropenia (25%), mucositis (22%) and vomiting (20%) were the most severe toxicities recorded (grade 3 and 4) during IC while mucositis (36%), dermatitis (28%), anemia (14%) and vomiting (14%) were the most pronouncing toxicities (grade 3 and 4) during CCRT. CONCLUSIONS: IC followed by CCRT treatment program is feasible, tolerable and safe. This strategy improved local control and distant disease control. However combined treatment program have failed to improve survival rates over the historical result of CCRT trials.     

TPF sequential therapy: when and for whom?

Concurrent chemoradiation is a standard approach for the treatment of locally advanced squamous cell carcinoma of the head and neck. However, sequentially administered chemotherapy and radiotherapy/chemoradiation may be an effective alternative for some patients. Although chemoradiation is a highly effective treatment approach, it is associated with high incidences of severe acute toxicities, including mucositis. In addition, late toxicities can cause long-term morbidity in a substantial proportion of patients. In a retrospective analysis of three Radiation Therapy Oncology Group trials, pharyngeal dysfunction was seen in 27% of patients and feeding tube dependence and laryngeal dysfunction were each seen in approximately 12% of patients. Sequential administration of chemotherapy and radiotherapy, with a doublet cisplatin and 5-fluorouracil (PF) induction chemotherapy regimen, is associated with less acute severe mucositis than concomitantly administered cisplatin and radiotherapy. The addition of the taxane docetaxel to PF has resulted in the highly active triplet induction regimen TPF. Data from randomized trials indicate that TPF sequential therapy may be an effective alternative to concurrent chemoradiation for some patients. TPF is well tolerated, although it is associated with a higher incidence of hematologic adverse events than with PF, including neutropenia and neutropenia-related complications. This may be managed by the use of prophylactic G-CSF and/or antibiotics. Patients suitable for treatment with a TPF-based sequential administration approach include those with a good performance status, no contraindication to cisplatin or taxanes, and locally advanced oropharyngeal, hypopharyngeal, or laryngeal cancer with a high tumor load.     

Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial.

PURPOSE: Recent studies have suggested the superiority of concurrent chemoradiotherapy and the efficacy of paclitaxel/carboplatin in advanced non-small-cell lung cancer (NSCLC). In view of those results, we sought to examine the safety and efficacy of administration of radiosensitizing paclitaxel twice weekly and carboplatin weekly with concurrent thoracic radiation therapy (XRT) followed by consolidation paclitaxel and carboplatin for stage III NSCLC in a multi-institutional phase II trial. PATIENTS AND METHODS: Induction chemoradiotherapy consisted of paclitaxel 30 mg/m2 delivered intravenously (IV) for 1 hour twice weekly for 6 weeks, carboplatin at a dose based on an area under the concentration-time curve (AUC) of 1.5 mg/mL x min, given IV once weekly for 6 weeks, and concomitant XRT of 1.8 to 2.0 Gy daily for a total of 61 Gy. Patients who achieved a complete response, partial response, or stable disease received two 21-day cycles of consolidation chemotherapy consisting of paclitaxel 200 mg/m2 IV for 3 hours and carboplatin at a dose based on an AUC of 6 mg/mL x min. RESULTS: Thirty-four patients were eligible. Their median age was 62 years (range, 39 to 73 years), 59% were female, 41% were male, 94% had a performance status of 0 or 1, 38% had stage IIIA NSCLC, and 62% had stage IIIB NSCLC. Common grade III and IV toxicities during the induction chemoradiation phase included esophagitis (38%) and neutropenia (12%). The most common adverse reaction during consolidation chemotherapy was grade III neutropenia in five patients (15%). The overall response rate was 71%, which was achieved in the induction phase. The median follow-up was 20 months, the median survival was 17 months, and 2-year actuarial survival rate was 40% (95% confidence interval, 20% to 65%). CONCLUSION: This regimen is tolerable and results are promising. We recommend further evaluation of this regimen in a phase III trial.