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 combined with coinstantaneous radiotherapy for locally advanced pancreatic cancer

Objective To evaluate the efficacy of stereotactic body radiotherapy combined with coinstantaneous gemcitabine, and gemcitabine alone for advanced pancreatic cancer. Methods 56 advanced pancreatic cancer patients were assigned into observation group, which accepted stereotactic body radiotherapy combined with coinstantaneous gemcitabine 500 mg/m², d1,d8. Other 50 patients were assigned into the control group which only accepted gemcitabine 1 000 mg/m², d1,d8,d15. Stereotactic body radiotherapy was delivered with a total dose of 4 000 4 500 cGy in 10 fractions. Results CT examinations were carried out 2 months after treatment. The response rate of the observation group and control group was 82% and 16% respectively, and the pain relief rate was 67% and 17% respectively. The time to progression of the observation group was 14 months, and was better than that of the control group（7.5 months,χ²= 7.31,P=0.032）.The median survival time of the observation group and control group was 15.8 months and 13.2 months, and the difference had no statistical significance(χ²= 3.28,P=0.082). Concolusion Stereotactic body radiotherapy combined with gemcitabine has a better overall response rate and a pain relief rate. It can prolong the time to progression, but can′t improve the overall survival.     

吉西他滨联合同步放疗治疗局部晚期胰腺癌疗效观察

 目的 评价立体定向放射治疗联合吉西他滨与吉西他滨单药治疗局部晚期胰腺癌的疗效.方法 治疗组56例胰腺癌行立体定向放疗联合吉西他滨单药化疗。对照组50例仅行吉西他滨单药化疗。立体定向放疗,总剂量4 000～4 500 cGy, 10次分割。同步化疗方案为吉西他滨500 mg/m² 第1、8天。对照组给予输注吉西他滨1 000 mg/m², 第1、8、15天结果治疗结束2个月后CT复查,治疗组及对照组有效率分别为82%、16%,疼痛缓解率分别为 67%、17%。疾病进展时间治疗组为14个月,优于对照组7.5个月,差异有统计学意义（χ²= 7.31,P=0.032）。中位生存期治疗组和对照组分别为15.8个月及13.2个月,差异无统计学意义（χ²= 3.28,P=0.082）。结论立体定向放射治疗联合吉西他滨治疗局部晚期胰腺癌较单纯化疗组有效率、疼痛缓解率高;能延长疾病进展时间,但未能改善总生存期。     

Low-dose gemcitabine concurrent with radiation therapy for locally advanced pancreatic carcinoma

We evaluated the efficacy and feasibility of low-dose gemcitabine concurrent with radiation as adjuvant therapy. Nine cases of locally far advanced unresectable pancreatic cancer were enrolled in this study. Intraoperative radiation was carried out in every case using eight or ten centimeter cones with a radiation dose of twenty to twenty five Gy. Postoperative radiation was two Gy per day on weekdays for five weeks. Low-dose gemcitabine (40 mg/m2) once a week was administered prior to radiation. A grade 3 adverse event occurred in three cases. CA19-9 decreased 60.1% and DUPAN-2, 52.6%. CT scan confirmed a necrotic change and a decrease of the tumor size. Average survival time was ten months. Peritoneal dissemination was the recurrence pattern. In conclusion, low-dose gemcitabine concurrent with radiation therapy may contribute to local control of the disease. However, peritoneal dissemination must be overcome to prolong survival.     

A phase I trial of Capecitabine+Gemcitabine with radical radiation for locally advanced pancreatic cancer

Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0–1. During RT, Gem was escalated from 20–50 mg m⁻² day⁻¹ (twice per week), and Cap 800–2000 mg m⁻² day⁻¹ (b.i.d, days 1–5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m⁻² day⁻¹ (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.     

Gemcitabine,paclitaxel, and radiation for locally advanced pancreatic cancer: a Phase I trial

PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of gemcitabine, paclitaxel, and concurrent radiation for pancreatic cancer. METHODS AND MATERIALS: Twenty patients with locally unresectable pancreatic cancer were studied. The initial dose level was gemcitabine 75 mg/m(2) and paclitaxel 40 mg/m(2) weekly for 6 weeks. Concurrent radiation to 50.4 Gy was delivered in 1.8 Gy fractions. The radiation fields included the primary tumor, plus the regional peripancreatic, celiac, and porta hepatis lymph nodes. RESULTS: Dose-limiting toxicities of diarrhea, dehydration, nausea, and anorexia occurred in 3 of 3 patients at the second dose level of gemcitabine, 150 mg/m(2)/week. An intermediate dose level of gemcitabine, 110 mg/m(2)/week, was added, but gastrointestinal toxicity and pulmonary pneumonitis were encountered. The MTD therefore was gemcitabine 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and concurrent radiation. Two of 11 patients treated at the MTD had Grade 3/4 toxicity. Four of 10 assessable patients treated at the MTD responded (40%), including one pathologic complete response. CONCLUSION: The maximum tolerated dosage of gemcitabine is 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and conventional 50.4 Gy radiation fields. A Phase II Radiation Therapy Oncology Group study is under way.     

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 II trial of primary radiation therapy and concurrent chemotherapy for patients with locally advanced pancreatic cancer

OBJECTIVES: Primary chemoradiotherapy for locally advanced pancreatic cancer (LAPC) may improve local control, curative resection rate and long-term survival. We performed a phase II study to evaluate toxicity and activity of primary radiation therapy and concurrent chemotherapy with gemcitabine (GEM) twice weekly in patients (pts) with LAPC. METHODS: From 6/1999 to 6/2003, 23 LAPC pts received GEM 100 mg/m2 twice weekly in the first 15 pts and 50 mg/m2 in the last 8 pts, concurrently with radiotherapy (1.8 Gy/day for a total dose of 45 Gy). RESULTS: The treatment was completed in 19/23 pts. Toxicities: G3-4 hematological toxicity occurred in 35 and 4% respectively; G3 nausea and vomiting and gastrointestinal toxicity in 30%. Clinical benefit was found in 10/18 pts (55%). Overall response: partial response rate 4/18 (22%); stable disease 13/18 (72%); progressive disease 1/18 (6%). Six pts underwent pancreaticoduodenectomy with extended lymphadenectomy (5/6 pts pT3, 1/6 pts microscopic cancer foci, 1/6 N+, 5/6 negative retroperitoneal margin). MEDIAN SURVIVAL: 14 months for the entire group, 12 months for unresected pts, 20 months for resected pts. CONCLUSIONS: The treatment with GEM twice weekly at 50 mg/m2 associated with radiotherapy (45 Gy) is feasible and permits to obtain clinical benefit in a good percentage of pts. Objective response, median survival, and local and systemic control are similar to other studies and need further improvement.     

Intraarterial cisplatin and concurrent radiation for locally advanced bladder cancer

Between 1983 and 1987 25 patients with invasive bladder cancer (16 stage tumor 3 (T3) and nine stage T4) were treated with intraarterial cisplatin and concurrent radical radiation (20/25) or intraarterial cisplatin, concurrent preoperative radiation, and cystectomy (5/25). One patient died from treatment-related toxicity. Other toxicities have been what one would expect from the individual treatment modalities except for a sensory sacral root neuropathy in 11 of 24 (46%) patients. Twenty-three of 24 (96%) patients achieved a complete response (CR) and the projected actuarial 2-year survival is 90%. Only one of the 23 complete responders has had an invasive local recurrence. The excellent complete local response and survival rates achieved warrant further study of the combination of intraarterial cisplatin and radiation as a bladder-preserving strategy.     

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis

Aims

Whether gemcitabine based chemoradiotherapy (GEM-based CRT) is superior to 5-fluorouracil based chemoradiotherapy (5-FU-based CRT) for locally advanced pancreatic cancer (LAPC) remains uncertain. The aim of the present study was to evaluate the effect of GEM-based CRT compared with 5-FU-based CRT.

Methods

Electronic database including Medline, Embase, Cochrane controlled trials register, PubMed (update to December 2010) and manual bibliography searches were carried out. A meta-analysis of all randomized clinical trials (RCTs) or other comparative studies comparing GEM-based CRT and 5-FU-based CRT were performed.

Results

Three RCTs and one retrospective comparative study including 229 patients were assessed. Meta-analysis showed survival advantage of GEM-based CRT compared with 5-FU-based CRT for 12-month (12-mo) survival rates (SRs) (RR = 1.54, 95% CI 1.05-2.26, p = 0.03). Moreover, there were also trends of benefit for SR after 6-months (RR 1.13, 95% CI 0.98-1.30, p = 0.09) and 24-months (24-mo: RR 2.41, 95% CI 0.90-6.48, p = 0.08), though the trends did not reach statistical significance. More frequent severe acute hematologic toxicities were found in the GEM-based CRT group.

Conclusions

The meta-analysis found that GEM-based CRT was better than 5-FU-based CRT in the treatment of LAPC, especially for 12-mo SRs. However, the acute toxicity should be carefully regarded.     

吉西他滨联合奥沙利铂治疗进展期胰腺癌(附40例)

目的:观察吉西他滨(择菲GEM)联合奥沙利铂(艾恒OXA)组成的GEMOX方案治疗进展期胰腺癌的有效性和安全性。方法:进展期胰腺癌40例,应用GEM800mg/m2静滴半小时,d1,d8;OXA60mg/m2静滴2小时,d2,d9;21天重复。至少接受2个周期的化疗,按照WHO标准进行评价。结果:观察化疗后肿瘤原发病灶的变化情况及化疗的不良反应。临床有效率为17.5%,具有较好的耐受性,不良反应主要有骨髓抑制和消化系统反应。结论:健择联合艾恒治疗进展期胰腺癌疗效较好,不良反应可以耐受。     

吉西他滨联合奥沙利铂治疗进展期胰腺癌（附40例）

目的：观察吉西他滨（择菲GEM）联合奥沙利铂（艾恒OXA）组成的GEMOX方案治疗进展期胰腺癌的有效性和安全性。方法：进展期胰腺癌40例,应用GEM800mg／m2静滴半小时,d1,d3;OXA60mg／m2静滴2小时,d2,d9;21天重复。至少接受2个周期的化疗,按照WHO标准进行评价。结果：观察化疗后肿瘤原发病灶的变化情况及化疗的不良反应。临床有效率为17．5％,具有较好的耐受性,不良反应主要有骨髓抑制和消化系统反应。结论：健择联合艾恒治疗进展期胰腺癌疗效较好,不良反应可以耐受。     

Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer

Purpose

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and feasibility of the combination of capecitabine and erlotinib with radiotherapy in this group of patients.

Experimental design

A traditional “3 + 3” dose escalation design was adopted in the study. A total of four dose levels were designed. For safety purpose, a minus I dose level (?I) was also planned. The ?I level consisted of capecitabine 600 mg/m² and erlotinib 50 mg daily, and the remaining four dose levels were as follows: level I: capecitabine 600 mg/m² bid (twice daily); level II: 700 mg/m² bid; level III: 825 mg/m² bid; and level IV: 925 mg/m² bid. Erlotinib was administered at 100 mg daily at all dose levels. Erlotinib and capceitabine were given continuously Monday through Friday concurrent with radiotherapy (50.4 Gy in 28 fractions).

Results

A total of 18 patients were consented. Fifteen patients were enrolled and completed therapy. No dose-limiting toxicity was observed. The most frequent side effects were lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes. The majority of the toxicities were grade 1 and 2. No objective response was observed. The median progression-free survival was 0.59 years (95 % CI 0.31–1.1), and the median overall survival was 1.1 years (95 % CI 0.62–1.59).

Conclusions

The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is well tolerated and feasible at the dose level of capecitabine 925 mg/m² bid and erlotinib 100 mg daily.     

EGFR inhibitors with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer

Currently, a combination of chemotherapy and radiotherapy is the standard treatment approach for locally advanced non-small cell lung cancer (NSCLC). However, the clinical outcomes are still disappointing, with the 5-year survival rate being only approximately 20%. Further improvement in treatment outcome for patients with locally advanced NSCLC will require the development of more effective combined-modality therapies. Increasing attention has focused on the integration of targeted agents into current therapies. Many preclinical studies in this area have targeted the epidermal growth factor receptor (EGFR) signaling pathway to increase radiosensitivity. The in vitro rationale for targeting EGFR and concurrent ionizing radiation is well established, but to date, rare clinical data could provide proof-of-principle. In this review article, we briefly discuss pre-clinical data and the rationale and report all the different published clinical trials focusing on efficacy and toxicity in order to clarify and to summarize the present state-of-the-art of this particular combination in NSCLC.     

Preoperative radiation with concurrent 5-fluorouracil continuous infusion for locally advanced unresectable rectal cancer

Background and Purpose: To determine the percentage of complete responders and the resectability rate for patients with locally advanced carcinoma of the rectum treated by 5-fluorouracil (5-FU) infusional chemotherapy and pelvic radiation.Materials and Methods: Between October 1992 and June 1996, 29 patients with a diagnosis of locally advanced unresectable rectal cancer received preoperative 5 FU by continuous intravenous infusion at a dose of 225 mg/m²/day concurrent with pelvic radiation (median 54 Gy/28 fractions). All patients were clinical stage T4 on the bases of organ invasion or tumor fixation. Median time for surgical resection was 6 weeks.Results: Median follow-up for the group was 28 months (range 5–57 months). Six patients were felt to be persistently unresectable or developed distant metastases and did not undergo surgical resection. Of the 29 patients, 23 proceeded to surgery, 18 were resectable for cure, 13 by abdominoperineal resection, 3 by anterior resection and 2 by local excision. Of the 29 patients, 4 (13%) had a complete response, and 90% were clinically downstaged. Of the 18 resected patients, 1 has died of his disease, 17 are alive, and 15 disease-free. The regimen was well tolerated; there was only one treatment-related complication, a wound dehiscence.Conclusion: The combination of 5 FU infusion and pelvic radiation in the management of locally advanced rectal cancer is well tolerated and provides a baseline for comparison purposes with future combinations of newer systemic agents and radiation.     

吉西他滨单药或与顺铂联合治疗胰腺癌的临床疗效评价

目的 评价吉西他滨单药以及与顺铂联合治疗局部晚期或转移性胰腺炎的疗效。临床受益反应,生存时间和毒性反应。方法 42例患者随机分为吉西他滨单药组（A组20例）和吉西他滨 顺铂联合组（B组22例）,A组;吉西他滨1000mg/m^2,每周1次,连用7周,休息1周;随后相同剂量每周1次,连用3周,休息1周,B组;吉西他滨1000mg/m^2,每周1次,连用3周,顺铂60mg/m^2,第15天给药,休息1周,每4周重复,边境用药3个周期。结果 42例患者中,可评价客观疗效者34例（A组16例,B组18例,可评价临床受益反应（CBR）者36例（A组16例,B组20例）,可进行毒性反应评估者40例（A组19例,B组21例）,A组：PR1例（6.3%)。MR4例（25.0%),SD7例（43.8%)。PD4例（25.0%)。B组;PR2例（11.0%)。MR3例（16.7%),SD8例（44.4%),PD5例（27.8%)。PR MR SD率A组为75.0%。B组为72.2%。CBR有效率A组为87.5%(14/16),B组为70.0%(14/20)。两组3个月生存率均为100%,6个月生存率分别为81.3%和61.6%。12个月生存率分别为31.3%和11.1%。B组Ⅲ、Ⅳ度血液学毒性反应发生率略高于A组,两组相比,差异无显著性。结论 吉西他滨单药以及与顺铂联合一线治疗局部晚期或转移性胰腺癌有一定的客观疗效。可明显改善患者的生活质量。延长了生存时间,患者耐受良好。     

Gemcitabine-based concurrent chemoradiotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer

Objective: To explore improved treatment by retrospectively comparing survival time of gemcitabine-basedconcurrent chemoradiotherapy (GemRT) versus chemotherapy (Gem) alone in patients with locally advancedpancreatic cancer (LAPC). Methods: From January 2005 to June 2010, 56 patients with LAPC from Subei People’sHospital were treated either with Gem (n=21) or GemRT (n=35). Gem consisted of 4-6 cycles gemcitabine alone(1000 mg/m2 on Days 1, 8, 15, 28-day a cycle). GemRT consisted of 50.4Gy/28F radiotherapy with concurrent 2cycles of gemcitabine (1000 mg/m2 on days of radiation 1, 8, 15, 21-day a cycle). Radiation was delivered to thegross tumor volume plus 1-1.5 cm by use of a three-dimensional conformal technique. The follow-up time wascalculated from the time of diagnosis to the date of death or last contact. Kaplan-Meier methodology wes usedto evaluate survival. Results: Patient characteristics were not significantly different between treatment groups.The disease control rate and the objective response rate of GemRT versus Gem was 97.1% vs 71.4%, 74.3%vs 38.1%. The overall survival (OS) was significantly better for GemRT compared to Gem (median 13 monthsversus 8 months; 51.4% versus 14.3% at 1 year, respectively). Conclusion: Radiation therapy at 50.4Gy with2 concurrent cycles of gemcitabine results in favorable rates of OS. Concurrent chemoradiotherapy should bethe first choice for patients with LAPC.