Paclitaxel and concurrent radiation for locally advanced pancreatic cancer

Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer.

Methods and Materials: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m² by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments.

Results: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%.

Conclusion: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.     

Gemcitabine concurrent with radiation for locally advanced pancreatic cancer

Gemcitabine (GEM) concurrent with radiation is clinically not well defined. We herein report four cases of chemo-radiotherapy against locally advanced pancreatic cancer using low-dose GEM concurrent with extra-beam radiation. A total of eight cases entered the study. Three were resected and five were non-resected cases. Intraoperative radiation was carried out in every case using an 8 or 10 centimeter cone with a radiation dose of 25 Gy. Postoperative radiation was 2 Gy per day on weekdays for 5 weeks. Four cases were concurrent with low-dose GEM (40 mg/m2) twice a week, whereas the other four were radiation only. With the use of GEM concurrent with radiation, tumor markers decreased more than 80 percent regardless of the tumor resection. CT scan confirmed a necrotic change and the decrease of the tumor size. In conclusion, low dose GEM concurrent with radiation therapy may be a promising therapeutic choice for the local control of advanced pancreatic cancers.     

Clinical investigation of weekly cisplatin and vinorelbine with concurrent radiation therapy for locally advanced non-small cell lung cancer

Concurrent combination therapy with chemotherapy(cisplatin(CDDP)and vinorelbine(VNR))and thoracic radiotherapy was administered to patients with unresectable locally advanced non-small cell lung cancer. The subjects were 19 patients with stage III non-small cell lung cancer, PS 0-1. They were able to undergo thoracic radiotherapy, had not received previous therapy, and had maintained main organ functions. CDDP(40mg/m / 2)and VNR(20mg/m2)were administered on days 1, 8, 22, and 29, and thoracic radiotherapy was performed every day except for those on which chemotherapy was conducted, 5 days a week at 2 Gy/day(total: 60 Gy). Four subjects were stage III A, 15 were stage III B, and their ages ranged from 42 to 75 years(median age: 65 years). The subjects were 18 males and 1 female, and concerning their histological types, 12, 5, and 2 were diagnosed squamous cell, adeno- and adenosquamous carcinoma, respectively. Regarding the therapeutic efficacy, 0, 14, and 5 subjects were clinically CR, cPR, and cSD, respectively, and their response rate was 73. 7%. The median survival time was 27. 2 months, and the one-year survival rate was 71. 2%. Concerning≥grade 3 adverse effects, 14 and 12 cases had leukocytopenia and neutropenia, respectively. However, no esophagitis was observed, and only one case experienced≥grade 3 nausea and vomiting. Radiation pneumonitis(≥grade 3)was observed in one case, but there was no severe liver or renal dysfunction, and no treatment-related death. It was suggested that this treatment reduces the occurrence of renal toxicity and digestive symptoms, and that a marked antitumor effect can be expected from its administration.     

A phase II study of intra-arterial cisplatin with concurrent radiation and erlotinib for locally advanced head and neck cancer

Background

Based on the convenient oral dosing of erlotinib and the promising results of biologic therapy, we undertook a phase II study with 21 patients with locally advanced (T3–4) lesions combining radiation with intra-arterial (IA) cisplatin and oral daily erlotinib for a 7-week therapy.

Methods

Treatment for the primary tumor and upper neck was given to a total dose of 70 Gy. Chemotherapy with IA cisplatin (150 mg/m²) was given on days 1, 8, 15, and 22 concurrently with radiotherapy. During the 7-week treatment period, patients were given erlotinib 150 mg/day.

Results

Overall survival is 63 %, and the relapse/persistent disease rate stands at 36.8 %. A total of 15.2 % of serious adverse event was considered related to erlotinib.

Conclusion

Our study and several others now demonstrate the feasibility of combining anti-epidermal growth factor receptor (EGFR) therapy with chemoradiation, hint at improved survival outcomes with reduced distant metastatic rates, and suggest that maintenance therapy with anti-EGFR agent may be beneficial.     

TP诱导联合DDP同期放化疗治疗局部晚期食管癌临床研究

  目的  研究不适手术的局部晚期食管癌患者行TP方案诱导化疗联合DDP同期放化疗的毒性及疗效。  方法  33例胸段食管鳞癌T₃N₀M_O~T₄N₂M₀期患者（不包括腹腔淋巴结转移）,第1天和第22天行TP方案诱导化疗,多西他赛（艾素）75 mg/m2, DDP 75 mg/m2。第43天开始放疗,采用三维适形放疗,总剂量60 Gy,2 Gy/次,5次/周。同期化疗:DDP 30 mg/m2,1次/周,放疗开始的第1、8、15、22、29、36天给药。  结果  诱导化疗Ⅳ级骨髓毒性为12.12%（4/33）,无Ⅲ级或以上的肝、肾毒性。同期放化疗骨髓毒性最高为Ⅲ级,红细胞、粒细胞、血小板Ⅲ级毒性分别为21.21%（7/33）、15.15%（5/33）、3.03%（1/33）,无Ⅱ级以上的肝肾毒性。Ⅲ级放射性食管炎为9.10%（3/33）,未发现Ⅲ级以上的放射性食管炎及Ⅰ级以上的急性放射性肺炎。治疗结束评价显效（CR+PR）84.85%（28/33）,稳定（SD）12.12%（4/33）,进展（PD）3.03%（1/33）;治疗后2个月评价显效（CR+PR）75.76%（25/33）,稳定（SD）9.10%（3/33）,进展（PD）15.15%（5/33）。全组死亡病例15例。1年生存率66.4%,最主要失败模式是局部失败46.67%（7/15）,局部+远处失败26.67%（4/15）。  结论  局部晚期食管癌患者行TP方案诱导化疗+DDP同期放化疗的毒性可以耐受,局部失败仍然是主要的失败模式。      

Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder

BACKGROUND:

The purpose of this study was to investigate the effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down‐staging of patients with locally advanced urothelial cancer (UC) of the bladder.

METHODS:

This was a retrospective cohort study of patients treated with radical cystectomy (RC) for clinical stage cT2‐T4, N any, M0 bladder UC at Strong Memorial Hospital from 1999 to 2009. The primary exposure variable was use of neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC. Secondary outcomes included other down‐staging end points in the bladder ( RESULTS: A total of 160 eligible patients were identified, of whom 25 were treated with neoadjuvant GC before RC (GC + RC) and 135 without neoadjuvant chemotherapy (RC only). Stage pT0 at cystectomy was found in 20% of patients in the GC + RC group and in 5% of patients in the RC group (adjusted risk difference [aRD] = 16%, P = .03). For other down‐staging end points, the estimated treatment effect was as follows (all point estimates favoring chemotherapy): P = .005); P = .004); P = .008); margins aRD = 8% (P = .41); nodes aRD = 4% (P = .74).

CONCLUSIONS:

Neoadjuvant GC was found to be capable of down‐staging UC in the bladder; however, no effect on disease in nodes was seen in this study. Cancer 2012;. © 2011 American Cancer Society.     

吉西他滨联合顺铂的新辅助化疗治疗局部晚期膀胱移行细胞癌

目的探讨吉西他滨联合顺铂(GC方案)的新辅助化疗方案治疗局部晚期膀胱移行细胞癌的临床疗效及毒性反应。方法 12例局部晚期膀胱移行细胞癌患者接受4个周期GC方案的新辅助化疗(吉西他滨1000mg/m2,第1、8天静脉滴注;顺铂20mg,第1～5天静脉滴注)。结果 12例均完成4个周期的GC方案化疗,总有效率58%,其中完全缓解2例,部分缓解5例,稳定3例,进展2例。6例患者化疗后行全膀胱切除术+回肠代膀胱术,3例经剖腹探查肿块无法切除而仅行放疗,2例患者因病情进展行姑息性化疗,1例患者拒绝手术治疗后仅行姑息性化疗。GC方案化疗的主要毒性为骨髓抑制,91%白细胞减少。结论吉西他滨联合顺铂是目前治疗局部晚期膀胱移行细胞癌有效、安全的新辅助化疗方案,为不能手术的局部晚期的膀胱移行细胞癌患者提供了新的治疗模式。     

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

Objective

To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer.

Methods

We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m² cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m²/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin.

Results

Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease.

Conclusion

CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated.     

健择联合顺铂合并放疗治疗进展期食管癌的临床研究

对41例初治进展期食管癌患者采用健择联合顺铂合并放射治疗。38例患者可以评估疗效和毒性。健择1000mg/m2,静脉滴入,d1、d8;顺铂20mg/m2,静脉滴入,d1~d4;同时合并放射治疗,每次2Gy,每周5次,共5周,总剂量为50Gy;化疗周期每21或28d重复。结果5例患者完全缓解,17例患者部分缓解,总有效率为58%;27例患者吞咽困难缓解,缓解率为71%;中位生存期为11·3个月;1、2年生存率分别为63%和45%;最常见的3、4度毒性是血小板下降(29%)、贫血(21%)、白细胞下降(24%)和食道炎(21%);无治疗相关死亡和3、4度的神经毒性。初步研究结果提示,健择加顺铂合并放疗方案治疗进展期食管癌耐受性好,疗效显著,值得临床广泛推广应用。     

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.     

Gemcitabine and cisplatin in locally advanced and/or metastatic bladder cancer

Although transitional cell carcinoma of the urothelium is chemosensitive, long-term disease-free survival is low. Accordingly, interest has focused on combining classically active agents like cisplatin with promising new drugs. Gemcitabine has evoked interest not only because of its intrinsic activity against this cancer, but also because of its effect of inhibiting repair of DNA that has been damaged by drugs like cisplatin. Four phase II studies have assessed the effect of a gemcitabine-cisplatin combination on advanced or metastatic bladder cancer. All the studies employed a gemcitabine dose of 1000 mg/m(2) given on days 1, 8 and 15, whereas the cisplatin dose and schedule varied, with total doses ranging from 70 to 105 mg/m(2). Overall response rates in these studies ranged from 42 to 66%, with complete responses from 15 to 28%. Toxicities, which were primarily haematological, were generally manageable. This promising two-drug combination has been compared with the standard MVAC regimen (methotrexate, vinblastine, doxorubicin, and cisplatin) in a randomised phase III trial and the results are eagerly anticipated.     

奈达铂对照顺铂同步放疗治疗中晚期宫颈癌的近期疗效及安全性评价

目的 比较奈达铂或顺铂同步根治性放疗治疗局部晚期宫颈癌的疗效和安全性。方法 回顾性分析2012年1月至2014年1月63例ⅠB2～ⅣA期宫颈癌患者的临床资料,其中奈达铂同步放疗组29例,顺铂同步放疗组34例。体外照射采用三维适形放疗,总剂量50 Gy／25 f;腔内照射A点后装总剂量30 Gy。顺铂40 mg／m2静滴,放疗开始后每周1次,共6次。奈达铂40 mg／m2静滴,放疗开始后每周1次,共6次。结果 奈达铂组获CR 19例、PR 9例、PD 1例,有效率（RR）为96.5％;顺铂组获CR 28例、PR 6例,RR为100.0％,两组RR的差异无统计学意义（P＞0.05）。奈达铂组2年无复发生存率和2年无转移生存率分别为93.1％和86.2％,顺铂组分别为91.2％和88.2％,差异均无统计学意义（P＞0.05）。两组主要不良反应为白细胞减少、血小板减少、恶心呕吐和放射性肠炎。奈达铂组3～4级恶心呕吐的发生率为17.2％,顺铂组为41.1％,差异有统计学意义（P＜0.05）;其他不良反应发生率的差异均无统计学意义（P＞0.05）。结论 奈达铂同步放疗治疗中晚期宫颈癌的疗效与顺铂相似,胃肠道反应较顺铂轻,安全性良好。     

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer

Aims: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42–75 years) were enrolled. Both cisplatin (40 mg/m²) and vinorelbine (20 mg/m²) were given on days 1 and 8 every 3 weeks. Beginning on day 2 of chemotherapy, thoracic radiotherapy was given for approximately 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results: Five of the 26 patients achieved a complete response, and 16 achieved a partial response for an overall response rate of 80.8% (95% confidence interval, 60.6–93.4%). The median survival time was 23 months (range, 4–43 months). Overall survival rates at 1 and 2 years were 80 and 56%, respectively. Hematologic toxicities included grade 3–4 neutropenia in 84.6% of patients, grade 3–4 thrombocytopenia in 3.8%, and grade 3–4 anemia in 61.5%. Two patients (7.7%) had grade 3 radiation esophagitis that resolved completely without dilation. Grade 3–4 radiation pneumonitis occurred in two patients (7.7%) and was treated with corticosteroids. Both patients had a good partial resolution of symptoms and radiographic abnormalities. There were no treatment-related deaths. The actual delivered dose intensities for both cisplatin and vinorelbine were 79.5%. Radiotherapy was completed in 96% of patients. Conclusion: Concurrent chemoradiotherapy with cisplatin and vinorelbine administered on a divided schedule is effective and well tolerated in patients with locally advanced NSCLC.     

Managing locally advanced bladder cancer

Locally advanced bladder cancer comprising tumor stages pT3a, pT3b, pT4a of the 1997 TNM system and/or involvement of regional lymph nodes can be cured by radical cystectomy. However, at least 50% of patients experience systemic progression within 5 years after surgery. In order to improve the fate of these patients, the administration of additional therapy has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy, as well as combined radiochemotherapy. Results from more than a dozen randomized Phase III trials on adjunctive chemotherapy, which include cystectomy as definite treatment have been reported. Whether neoadjuvant or adjuvant systemic chemotherapy is the superior form of adjunctive therapy for locally advanced bladder cancer continues to be a matter of dispute.     

Managing locally advanced bladder cancer

Locally advanced bladder cancer comprising tumor stages pT3a, pT3b, pT4a of the 1997 TNM system and/or involvement of regional lymphnodes can be cured by radical cystectomy. However, at least 50% of patients experience systemic progression within 5 years after surgery. In order to improve the fate of these patients, the administration of additional therapy has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy, as well as combined radiochemotherapy. Results from more than a dozen randomized Phase III trials on adjunctive chemotherapy, which include cystectomy as definite treatment have been reported. Whether neoadjuvant or adjuvant systemic chemotherapy is the superior form of adjunctive therapy for locally advanced bladder cancer continues to be a matter of dispute.     

Localized and locally advanced bladder cancer

Opinion statement Localized and locally advanced bladder cancer represents a heterogeneous spectrum of diseases with different biologic and clinical behavior. It varies with respect to invasive potential, propensity for metastases, and sensitivity to chemotherapy. Although several significant surgical advances have been made over the past 20 years in the treatment of muscle-invasive bladder cancer, resulting in decreases in perioperative morbidity and mortality and improvement of quality of life in patients with continent urinary diversions, the natural history of the disease has remained unaltered. Advances in chemotherapy for metastatic disease have prompted trials of systemic therapy in patients with early stage, high-risk disease administered before or after local therapy consisting of cystectomy or radiotherapy. The data available from nonrandomized and randomized trials have not definitively established the exact role of neoadjuvant chemotherapy and its impact on survival. Even if neoadjuvant chemotherapy does not improve survival, preliminary data suggest that bladder preservation may be possible in selected patients and that such combined therapy will hopefully lead to better patient management. The trials of post-operative chemotherapy provide insufficient evidence to support the routine use of adjuvant chemotherapy in clinical practice as a result of small sample size, confusing analyses, and the reporting of questionable conclusions. New large-scale, multicenter trials are imperative to provide convincing results. A better understanding of the micro-biology of bladder cancer will influence the search for new therapeutic modalities. Molecular-targeted small-molecule therapy and monoclonal antibodies have begun to dominate contemporary studies.