Induction Gemcitabine Plus Concurrent Gemcitabine and Radiotherapy for Locally Advanced Unresectable or Resected Pancreatic Cancer

AimsTo determine the efficacy of induction gemcitabine followed by biweekly gemcitabine concurrent with radiotherapy for locally advanced pancreatic cancer.Materials and methodsBetween March 2001 and August 2009, 90 patients with unresectable (78) or resected (12) pancreatic cancer were treated with a standard treatment policy of induction gemcitabine (seven doses of weekly gemcitabine at 1000 mg/m²) followed by concurrent radiotherapy (52.5 Gy) and biweekly gemcitabine (40 mg/m²).ResultsAfter induction gemcitabine, 17.8% of patients did not proceed to chemoradiotherapy, due to either disease progression, performance status deterioration or gemcitabine toxicity. Of the patients who received chemoradiotherapy, 68.9% completed the course of 52.5 Gy, whereas 79.7% received more than 45 Gy. Chemoradiotherapy was stopped early due to treatment toxicity in 22.9% of patients. On intention to treat analysis, the median overall survival was 12.7 months in the locally advanced group and 18.2 months in the resected group. On multivariate analysis for the unresectable patients, a larger gross tumour volume was a significant poor prognostic factor for overall survival and local progression-free survival.ConclusionThis large series confirms, in a standard practice setting, similar efficacy and tolerability of treatment as previously reported in our phase I–II study. The benefit to patients with a gross tumour volume >48 cm³ may be limited.     

A phase II study of induction chemotherapy with gemcitabine plus S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer

Purpose

The aim of this study was to investigate the feasibility and efficacy of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer.

Methods

Patients with locally advanced unresectable pancreatic cancer received four cycles of induction chemotherapy consisting of 30-min intravenous infusions of gemcitabine 1,000 mg/m² on days 1 and 8 and oral S-1 40 mg/m² twice daily on days 1–14 of a 21-day cycle. Those without disease progression received chemoradiotherapy of 30 Gy in ten fractions with 250 mg/m² of gemcitabine on days 1 and 8.

Results

A total of 20 patients were treated. Median follow-up time was 431 days (range 133–1,014 days). Four cycles of induction chemotherapy were completed in 18 patients, and 16 patients received chemoradiotherapy, which was completed without delay in all. Grade 3–4 toxicities associated with induction chemotherapy were neutropenia (50%); anemia (20%); thrombocytopenia (10%); febrile neutropenia (5%); nausea (10%); anorexia (10%); and vomiting, fatigue, dehydration, stomatitis, and rash (5%). Grade 3–4 toxicities among those receiving chemoradiotherapy were neutropenia (13%) and anemia (6%). Median progression-free survival was 8.1 months. Median overall survival was 14.4 months, with a 1-year survival rate of 54.2%.

Conclusions

The regimen of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy used in the present study demonstrated promising activity in locally advanced pancreatic cancer. Further consideration of radiation schedule and duration of induction chemotherapy is required to enhance the efficacy of this strategy.     

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.     

Intensified Neoadjuvant Chemotherapy with Nab-Paclitaxel plus Gemcitabine Followed by FOLFIRINOX in a Patient with Locally Advanced Unresectable Pancreatic Cancer

The prognosis of patients with locally advanced pancreatic cancer can be improved if secondary complete (R0) resection is possible. In patients initially staged as unresectable this may be achieved with neoadjuvant treatment which is usually chemoradiotherapy based. We report the case of a 46-year-old patient with an unresectable, locally advanced pancreatic cancer (pT4 Nx cM0 G2) who was treated with a sequential neoadjuvant chemotherapy regimen consisting of 2 cycles of nab-paclitaxel plus gemcitabine followed by 4 cycles of FOLFIRINOX. Neoadjuvant chemotherapy resulted in secondary resectability (R0 resection). After 2 cycles of nab-paclitaxel plus gemcitabine, the patient already had a complete metabolic remission as measured by integrated fludeoxyglucose (¹⁸F) positron emission tomography and computerized tomography. After a follow-up of 18 months the patient is alive without progression of disease. We propose to assess the clinical benefit of sequencing the combinations nab-paclitaxel plus gemcitabine and FOLFIRINOX as neoadjuvant therapy for patients with locally advanced and initially unresectable pancreatic cancer in a controlled clinical trial.Key Words: Pancreatic cancer, Locally advanced disease, Neoadjuvant chemotherapy, Nab-paclitaxel, Gemcitabine, 5-Fluorouracil, Folinic acid, Oxaliplatin, Irinotecan     

Phase II study of gemcitabine combined with radiation therapy in patients with localized,unresectable pancreatic cancer

BACKGROUND AND OBJECTIVES: Gemcitabine is an active agent in pancreatic cancer, with known radiosensitizing properties. Therefore, a phase II study was conducted to evaluate the efficacy of gemcitabine combined with radiation therapy in patients with localized unresectable adenocarcinoma of the pancreas. METHODS: Weekly gemcitabine at a dose of 1,000 mg/m(2) for 7 weeks was given as an induction phase. Patients who showed both clinical benefit response (CBR) and reduced or stable tumor size on computed tomography (CT) scan entered the chemoradiotherapy phase of the treatment. This consisted of gemcitabine 400 mg/m(2) weekly x3 every 28 days for 2 cycles, given concurrently with radiotherapy, for a total dose of 50.4 Gy in 28 fractions. After completion of radiotherapy, gemcitabine was continued as maintenance. RESULTS: Twenty patients entered this study. Ten patients (50%) achieved CBR to gemcitabine in the induction phase; these patients had no objective tumor progression and were therefore enrolled in the chemoradiotherapy phase. Four patients (20%) had a partial response, and three patients (15%) underwent pancreatectomy. Two patients had negative surgical margins, and in one patient histologic examination of the residual mass showed only fibrosis. The median survival for the entire group was 8 months, and the median survival has not yet been reached for the chemoradiotherapy group. CONCLUSIONS: Treatment with gemcitabine concomitant with radiation therapy according to the present schedule is well tolerated and can provide prolonged CBR and disease stabilization in patients with localized, unresectable pancreatic cancer.     

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m(-2), 30-min infusion). Maintenance gemcitabine (1000 mg m(-2) weekly x 3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.     

Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer

Neoadjuvant therapy is increasingly becoming a valid treatment option for patients with locally advanced pancreatic cancer (LAPC). In borderline resectable disease, neoadjuvant therapy is employed to improve the probability of margin-clear resections. In non-metastatic, non-resectable pancreatic cancer, treatment primarily aims to induce disease control, but may achieve conversion to surgical resectability in some patients. Several treatment modalities including chemotherapy, chemoradiotherapy (CRT) or the sequential use of both have been investigated in numerous, mostly small and non-randomized studies. Nevertheless, there is a consistent finding that neoadjuvant therapy can induce resectability in up to 30%–40% of LAPC patients. Once resection has been achieved, overall survival appears to be comparable to that observed for primarily resectable patients. Thus, patient selection evolves as an important aspect of neoadjuvant therapy; retrospective analyses identified induction chemotherapy as an appropriate tool to define LAPC patients who may benefit most from subsequent treatment with CRT. The clinical importance of induction chemotherapy may further increase once highly active protocols such as the FOLFIRINOX or the gemcitabine plus nab-paclitaxel regimen are introduced into novel multimodality treatment concepts.     

局部晚期非小细胞肺癌同步放化疗并序贯化疗与单纯序贯放化疗的对比研究

目的 观察局部晚期非小细胞肺癌（NSCLC）接受调强放疗（IMRT）联合同步吉西他滨和卡铂方案（GC）化疗与序贯放化疗的近、远期疗效和不良反应。方法 回顾性分析不能进行手术治疗和拒绝手术治疗的局部晚期NSCLC患者65例,其中同步放化疗并序贯化疗组给予IMRT同步联合GC治疗者32例,单纯序贯放化疗组为33例给予IMRT后序贯GC治疗。通过统计分析比较两组之间的近期有效率、远期生存率和不良反应。结果 两组均完成治疗,随访率100%,同步放化疗并序贯化疗组近期有效率为75%,单纯序贯放化疗组为66.7% ,两组比较差异有统计学意义（P＜0.05）。两组1、3年生存率相比较,同步放化疗并序贯化疗组为68. 2% 、20. 5% ;单纯序贯放化疗组为 50. 1% 、11.3%;同步放化疗并序贯化疗组明显优于单纯序贯放化疗组（P＜0.05）。两组不良反应情况对比,差异无统计学意义（P＞0.05）。结论 IMRT同步联合GC方案并序贯化疗治疗局部晚期NSCLC,可以提高患者的远期生存率且不良反应可耐受。     

Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer: a feasibility study

Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.     

吉西他滨联合适形放疗与吉西他滨联合顺铂对局部晚期胰腺癌的疗效比较

目的：比较吉西他滨联合适形放疗与吉西他滨联合顺铂对局部晚期胰腺癌的疗效。方法：前瞻性分析了2002年3月-2005年8月收治的56例局部晚期胰腺癌患者的疗效，其中26例采用吉西他滨联合适形放疗（放化组），30例采用吉西他滨联合顺铂（化疗组）。结果：可评估病例54例，放化组有效率（CR＋PR）为68．O％，化疗组有效率（CR＋PR）为37．9％，两组差异有统计学意义（P=0．0275）。放化组和化疗组的6月生存率分别为84．O％和62．1％（P=0．0728）；12月生存率分别为64．O％和37．9％（P=0．0561）。两组差异无统计学意义。放化组和化疗组的临床获益率（CBR）分别为84．0％和69．0％，两者差异无统计学意义（P=0．1976）。放化组和化疗组的严重不良事件总发生率分别为36．0％和44．8％，无统计学差异（P=0．5103）。结论：在近期疗效方面，吉西他滨联合适形放疗的近期疗效优于吉西他滨联合顺铂；而远期生存率，吉西他滨联合适形放疗虽然显示出一定的优势，但无统计学意义，二者在CBR和严重不良事件发生率无明显差异。     

Systemic chemotherapy and chemoradiotherapy for advanced pancreatic cancer

Currently, we are able to use S-1 with gemcitabine and erlotinib, as well as gemcitabine alone, as first-line therapy for advanced pancreatic cancer. In addition, a clinical trial of FOLFIRINOX is underway in Japan. On the other hand, chemoradiotherapy is considered to be one of the treatments of choice for locally advanced pancreatic cancer. This review summarizes current knowledge about non-surgical treatment for advanced pancreatic cancer, mainly based on the results of recent clinical trials.     

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study

PURPOSE: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2)) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer.     

局部晚期乳腺癌改良根治术后多西他赛同步放化疗的放射性不良反应观察*

目的：对比观察局部晚期乳腺癌改良根治术后多西他赛同步放化疗与序贯放疗的放射性不良反应,评估多西他赛同步放化疗模式的安全性、可行性。方法：收集2009年1 月至2014年12月广西医科大学第四附属医院155 例女性乳腺癌病例,患者均行乳腺癌改良根治术,病理诊断为乳腺浸润性导管癌,TNM 分期为pT3～4pN1～3cM0 或p 任意TpN 2～3cM0。采用氟尿嘧啶+ 表柔比星+ 环磷酰胺（FEC ）化疗方案后,密闭信封法随机分为同步组（多西他赛化疗时同步放疗）78例、序贯组（多西他赛化疗完成后放疗）77例,观察两组放射性不良反应及近期疗效。结果：中位随访39（16～62）个月。同步组和序贯组的放射性不良反应轻微,均无3～4 级放射性皮肤反应、症状性心肺放射损伤。1～2 级放射性皮肤反应同步组的发生率为89.7%（70/ 78）、序贯组为88.3%（68/ 77）,两组比较差异无统计学意义（P > 0.05）。 3 年无复发生存率同步组为92.3%（72/ 78）,序贯组为81.8%（63/ 77）,两组比较差异具有统计学意义（P = 0.046）。 结论：局部晚期乳腺癌改良根治术后多西他赛同步放化疗的放射性不良反应轻微,与序贯治疗比较提高了患者的3 年无复发生存率,安全可行,可作为局部晚期乳腺癌的治疗选择。     

Treatments of pancreatic cancer from the standpoint of medical oncology

The early diagnosis of pancreatic cancer is difficult because of the lack of specific early symptoms,and surgery with curative intent can be performed in only 20% of patients. Chemotherapy for unresectable pancreatic cancer has been advancing ever since gemcitabine (GEM) was confirmed to provide a survival advantage in patients with advanced pancreatic cancer. For more than 20 years, the standard treatment for locally advanced diseases has been chemoradiotherapy using 5-FU, but more effective chemotherapy regimens are required. New standard treatments for locally advanced pancreatic cancer, including GEM chemotherapy and chemoradiotherapy using new agents, should be investigated. Several randomized clinical trials comparing GEM-based chemotherapy and GEM alone for the treatment of unresectable pancreatic cancer have been conducted, but a new standard chemotherapy regimen superior to GEM alone has not established. In Japan, phase II studies of S-1 or a combination of GEM and S-1 have produced promising survival rates, and a large phase III study using GEM and S-1 is necessary to establish the standard chemotherapy. Furthermore, second-line chemotherapy regimens for use after GEM chemotherapy should be investigated to improve the survival of patients with advanced pancreatic cancer.     

A new cisplatin/gemcitabine schedule in locally advanced (IIIB) and metastatic (IV) non-small cell lung cancer: relationship between dose-intensity and efficacy. A phase II study

BACKGROUND: Cisplatin/gemcitabine are one of the "standard" chemotherapy schedules in locally advanced and metastatic NSCLC cancer. A number of trials documented that omission of gemcitabine on day 15 and reduction of cisplatin up to 70 mg/mq are equivalent in term of response rates to "classic" administrations on days 1, 8 and 15 with cisplatin 100 mg/mq. The aim of this study was to confirm this evidence and to demonstrate that a further reduction of gemcitabine dose-intensity may be performed with the same efficacy on response. PATIENTS AND METHODS: Fifty untreated patients with locally advanced and metastatic NSCLC entered the study: 24 stage IIIB and 26 stage IV. The median age was 65 years (range 32-76); 44 males and 6 females Genicitabine was administered 1000 mg/mq weekly on days 1 and 8 followed by a 2-week rest and cisplatin 80 mg/mq on day 2 of each 28-day-cycle. RESULTS: Forty-five patients were evaluable for response and all for toxicity. The overall response rates were 35.5% with 16 partial responses (95% Confidence Interval: 32%-61%). Most of the objective responses were seen in IIIB patients (56% of the stage IIIB and 44% of the stage IV patients responded). According to the intent-to-treat-principle, the response rates were 32% (16 out of 50 patients). The median dose-intensity of gemcitabine and cisplatin was respectively 477.6 mg/mq/week (481.4 for responders) and 19.5 mg/mq/week (19.9 mg/mq for responders). The median response duration was 5 months (range 1-18) and the median time to progression was 5 months (1-21); median survival was 9 months (range 2-31). The main toxicity was haematological: thrombocytopenia grade IV in 5 patients (10%) and grade III in 11 patients (22%); neutropenia grade III-IV in 4 patients (8%); grade III anemia in 3 (6%). Asthenia was the most significant non-haematological toxicity and was observed in 19 patients (38%). CONCLUSION: This trial confirmed the efficacy of a schedule with 2 administrations of gemcitabine (on days 1, 8) and a cisplatin dose on day 2 lower than 100 mg/mq. Moreover, the same efficacy was obtained with a median-dose intensity of cisplatin and gemcitabine lower than planned in a 21-day-schedule. For safety and low toxicity, we think that this schedule provides another chance to treat patients with non-small cell lung cancer, especially the elderly or patients with coexistent medical illnesses.     

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.     

SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)

Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.     

局部进展期胰腺癌的多学科综合治疗

胰腺癌是恶性程度高且预后极差的消化系统肿瘤。对可手术切除的局限性胰腺癌,因其术后局部复发儿率也较高,故建议采用以手术为主的多学科综合治疗。外放射治疗是无法手术胰腺癌的主要治疗手段。对无法切除的局部进展期肿瘤,主要采用局部外放射治疗联合全身化疗的多学科综合治疗。Ⅲ期随机临床研究结果已经证实,同期联合放化疗较单一放射治疗对患者的生存具显著优势。与放射治疗同步应用的化疗药物目前主要包括5-FU、卡培他滨与吉西他滨等。同期联合放化疗中应用多药联合化疗方案可明显增加治疗相关的不良反应,但临床研究结果并未显示多药方案对疗效及患者预后有所助益。放疗技术目前推荐三维适形放射治疗或调强放疗（IMRT）。靶区范围建议包括临床影像检查可见肿瘤外放安全边界,对未被侵及的淋巴引流区域不行预防性照射。IMRT不仅可减低周围正常组织的照射剂量,还可提高肿瘤靶区的照射剂量,实现剂量递增。     

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.