Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer.

BACKGROUND: The aim of this study was to determine the activity of the combination of cisplatin, gemcitabine and 5-fluorouracil (5-FU) as therapy for metastatic or locally advanced inoperable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic pancreatic adenocarcinoma received first-line chemotherapy comprising cisplatin (20 mg/m2 on days 1, 8, 15, 22, 29 and 36), gemcitabine (1000 mg/m2 on days 1, 8, 29 and 36) and 5-FU (200 mg/m2 as continuous infusion on days 1-42) every 56 days. RESULTS: A total of 34 patients were studied. Eighty courses were administered (median two courses per patient). Among 32 patients evaluable for response, two patients had a complete response and four a partial response for an overall response rate of 19% (95% confidence interval 7% to 36%). Thirteen patients had stable disease (40%) and 13 progressed. Median progression-free survival was 4.7 months, median survival 9.0 months and 26% of patients achieved 1-year survival. Ten of 25 patients (40%) with pain at presentation had a sustained reduction of analgesic consumption. The principal grade 3/4 toxicities were neutropenia, thrombocytopenia, anaemia and mucositis, occurring in 24%, 21%, 9% and 3% of patients. CONCLUSION: This schedule seems well tolerated and active in pancreatic cancer and worthwhile of further evaluation.     

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC)

This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m⁻² per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m⁻² day⁻¹ for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon''s optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5–16% and 2–22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25–101 weeks) for GEM and 26 weeks (range 16–46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2–65 weeks) and 18 weeks (range 4–51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1–101 weeks) and 30 weeks (1–101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.     

A phase I/II study of combination chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer

BACKGROUND: In an effort to improve efficacy of single-agent gemcitabine in pancreatic cancer, several studies have examined the effects of 5-FU combined with gemcitabine. However, no studies to date have been performed in Japanese patients. We thus conducted a phase I/II study of gemcitabine and infusional 5-FU in Japanese patients to determine a recommended dosage for this combination and clarify efficacy and toxicity. METHODS: Phase I evaluated the frequency of dose limiting toxicity of two 5-FU dosages (400 and 500 mg/m(2)/day) infused continuously over 5 days combined with gemcitabine 1000 mg/m(2) x 3 every 4 weeks. Results from phase I determined the recommended dosage to be examined in phase II for effect on survival period, clinical benefit response (CBR), tumor response and safety. RESULTS: A total of 34 chemo-naive patients were entered into the study. All had a Karnofsky performance of > or =50 points and distant metastases. Dose limiting toxicities in phase I determined the recommended 5-FU dosage at 400 mg/m(2)/day. Grade 3-4 hematological toxicities (neutropenia, leukopenia and thrombocytopenia) were the most common severe toxicities. For the 28 patients administered the recommended dosage, 1-year survival rate was 14.3%, median survival time 7.1 months and progression free survival 3.2 months. Seven patients achieved a 25% overall response rate and three showed 27.3% improvement in CBR. CONCLUSION: Although a meaningful survival benefit over single-agent gemcitabine was not demonstrated, 5-FU 400 mg/m(2)/day infused continuously over 5 days in combination with gemcitabine 1000 mg/m(2) x 3 every 4 weeks appeared to be a moderately effective palliative treatment with low toxicity in Japanese patients with metastatic pancreatic cancer.     

Phase II trial of bimonthly leucovorin, 5-fluorouracil and gemcitabine for advanced pancreatic adenocarcinoma (FOLFUGEM)

Background:Gemcitabine alone or 5-fluorouracil (5-FU) according to several schedules are used for palliation of metastatic and locally advanced (LA) pancreatic adenocarcinoma. This study was designed to test the efficacy of the leucovorin–5-FU and gemcitabine combination. Patients and methods:This phase II trial combined a simplified bimonthly LV5FU2 with gemcitabine: leucovorin 400 mg/m² in a two-hour infusion, followed by 5-fluorouracil 400 mg/m² bolus and 2 or 3 g/m² continuous infusion over 46 hours; gemcitabine 1 g/m² was infused over 30 min on day 3 after 5-FU. Treatment was repeated every two weeks. Gemcitabine dose could be increased (250 mg/m² every two cycles up to 1500 mg/m²) in the absence of NCI-CTC toxicity >2. Results:Among the 62 patients included in this study, 22 had LA and 40 had metastatic disease. Objective response rate for the 54 patients with measurable disease was 25.9% (95% confidence interval (CI): 14%–37.8%) and 22.6% (95% CI: 12%–33.2%) in the intent-to-treat population; the clinical benefit rate for the 59 assessable patients was 49.2%. Median progression-free survival and median overall survival were 4.8 and 9 months, respectively, with 32.3% of patients alive at 1 year. The most frequent toxicity (grade 3–4) was neutropenia (56.5%) usually asymptomatic (1.1% febrile neutropenia), but requiring decreases of 5-FU and gemcitabine doses. Unexpected complete alopecia occurred in 97% of patients. Conclusions:Palliative effects, response rate and survival observed in this multicenter study seem to be superior to those obtained with gemcitabine or 5-FU alone, despite a limiting hematological toxicity.     

Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Group study.

BACKGROUND: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. PATIENTS AND METHODS: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle. RESULTS: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. CONCLUSIONS: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.     

Phase II trial of combined regional hyperthermia and gemcitabine for locally advanced or metastatic pancreatic cancer

Purpose: Despite advances in cancer therapy, treating pancreatic cancer remains one of the major challenges in the field of medical oncology. We conducted this phase II study to evaluate the efficacy and safety of regional hyperthermia combined with gemcitabine for the treatment of unresectable advanced pancreatic cancer.

Methods: Eligibility criteria included histologically proven, locally advanced or metastatic pancreatic cancer. Gemcitabine was administered intravenously at a dose of 1000?mg/m² on days 1, 8, and 15 every 4 weeks. Regional hyperthermia was performed once weekly, 1 day preceding or following gemcitabine administration. The primary end point was the 1-year survival rate. Secondary objectives were determination of tumour response and safety.

Results: We enrolled 18 patients with advanced pancreatic cancer between November 2008 and May 2010. The major grade 3–4 adverse events were neutropenia and anaemia; however, there were no episodes of infection. The objective response rate (ORR) and disease control rate (ORR + stable disease) were 11.1% and 61.1%, respectively. Median overall survival (OS) was 8 months, and the 1-year survival rate was 33.3%. Median OS of patients with locally advanced pancreatic cancer was 17.7 months.

Conclusions: Regional hyperthermia combined with gemcitabine is well tolerated and active in patients with locally advanced pancreatic cancer.     

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。     

Treatment of advanced pancreatic cancer with epirubicin, 5-fluorouracil and l-leucovorin: A phase II study

Background: Preclinical data suggest that the levorotatory isomer ofleucovorin (l-LV) can augment the cytotoxic effects of 5-fluorouracil (5-FU)more effectively than racemic LV. A phase II study was initiated to evaluatethe effect of a combination of the pure L-isomer of LV and 5-FU along withepirubicin in patients with advanced pancreatic cancer.Patients and methods: Twenty-eight consecutive, previously untreatedpatients with measurable metastatic adenocarcinoma of the pancreas wereenrolled in this study. Treatment consisted of epirubicin 50 mg/m² onday 1 and 5-FU 400 mg/m² plus l-LV 100 mg/m²both administered on days 1 to 5. Treatment cycles were repeated every fourweeks for a total of six months unless progressive disease was documentedearlier. The study endpoints were survival, toxicity, objective response aswell as palliative beneficial effects of the regimen in terms of performancestatus, body weight and pain.Results: Six patients had a partialresponse (21%; 95% CI, 8% to 44%) and 10(36%) stable disease (35%), while the remaining 12 patients(43%) progressed during treatment. The median time to treatmentfailure was 2.9 months (range 1.2–13.7 months), and the mediansurvival time was six months (range, 1.8–19 months), with threepatients (11%) being alive after one year. Beneficial palliativeeffects in terms of performance status, body weight and/or pain were seen in12 of 28 patients (43%): an improvement in performance status wasrecorded in four patients, pain was attenuated and/or analgetic consumptionreduced by 50% in eight patients, and five patients had weightgain of >5% of their pretreatment body weight.Treatment-associated side effects were generally mild to moderate. Severeadverse reactions included (asymptomatic) granulocytopenia in five,mucositis and/or diarrhea WHO grade 3 in four patients.Conclusion: Our data suggest that epirubicin plus 5-FU andl-LV is a tolerable regimen that has some positive effects in the treatmentof pancreatic cancer. Since this regimen, however, is unlikely to offer anymajor therapeutic advantage compared to monochemotherapy or othercombination regimens, the search for novel and more effective cytotoxicagents must continue.     

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。     

吉西他滨加低剂量5-氟尿嘧啶持续静脉输注治疗晚期原发性肝癌

目的:评价吉西他滨加低剂量5-氟尿嘧啶(5-Fu)持续静脉输注治疗晚期原发性肝癌(PHC)患者的疗效、临床受益反应(clinicalbenefit response,CBR)以及不良反应。方法:l5例晚期PHC患者,采用吉西他滨800-1000mg/m2,静滴,d1,8,5-Fu250mg/(m2.day)经锁骨下静脉持续输注12天,21天为一周期。结果:15例患者中,13例可以评价疗效,其中2例PR,6例SD,5例PD。患者的肿瘤进展时间(TTP)为1-6.2个月,中位TTP3.2个月。CBR率为60%(9/15)。主要毒副反应为骨髓抑制,Ⅲ度-Ⅳ度贫血3例(20%),Ⅲ度粒细胞减少和血小板减少各2例(13.3%)和1例(6.7%)。消化道反应较轻,Ⅲ度腹泻和口腔粘膜炎各1例(6.7%)。结论:吉西他滨加低剂量5-Fu持续静脉输注治疗晚期原发性肝癌有一定的疗效,CBR率较高,毒副反应可以耐受,在晚期PHC尚无特别有效治疗措施的情况下,值得临床试用。     

A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer.

BACKGROUND: Oxaliplatin (OXA) significantly enhanced the antitumour activity of 5-fluorouracil (FUra) in patients with advanced colorectal cancer and displayed radiosensitising properties in preclinical studies. This study was thus performed to test the feasibility, identify the recommended doses (RDs) and explore preliminarily the clinical activity of weekly OXA and infused FUra combined with preoperative pelvic radiotherapy. PATIENTS AND METHODS: Forty-six patients with recurrent or locally advanced (cT3-4 and/or N+) adenocarcinomas of the mid-low rectum were treated with escalating doses of OXA (25, 35, 45, 60 mg/m2, weekly for 6 weeks) and FUra (200-225 mg/m2/day, 6-week infusion) concurrent to preoperative pelvic radiotherapy (50.4 Gy/28 fractions). The RDs for the phase II part of the study were immediately below the level resulting in dose-limiting toxicities in more than one third of the patients, or corresponded to the last planned dose level. RESULTS: In the escalation phase, dose-limiting toxicities only occurred in one patient at the fourth level and one of six patients treated at the last planned dose level (grade III diarrhoea). OXA 60 mg/m2 and FUra 225 mg/m2/day are therefore the RDs for the regimen. Among 25 patients globally treated at these doses (phase II part), the incidence of grade III diarrhoea was 16% with no grade IV toxicity. Neurotoxicity did not exceed grade II (12%). All patients completed radiotherapy and were operated on as scheduled. Twenty-one of 25 patients had the tumour down-staged after chemoradiation with seven (28%) pathological complete responses and 12 (48%) residual tumours limited to ypT1-2N0. CONCLUSIONS: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.     

Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer.

BACKGROUND: Oxaliplatin shows preclinical activity in many cancer cell lines that are resistant to cisplatin, and also has synergism with 5-fluorouracil (5-FU). We undertook this study to evaluate the efficacy and toxicities of a combined oxaliplatin, 5-FU and leucovorin (LV) continuous infusion regimen in patients with advanced gastric cancer who progressed during or after treatment with 5-FU and platinum compounds. PATIENTS AND METHODS: Twenty-six patients with advanced gastric cancer, whose disease progressed while receiving, or after discontinuing, chemotherapy with a 5-FU and platinum regimen, were enrolled in this study. Treatment comprised oxaliplatin (85 mg/m2 on day 1) as a 2-h infusion followed by bolus 5-FU (400 mg/m2 on day 1), and 48-h infusion of 5-FU 2.4-3.0 g/m2 concurrently with LV 150 mg/m2. Cycles were repeated at 2-week intervals. RESULTS: Of the 23 evaluable patients, there were six partial responses (response rate 26%). All responding patients were among those who entered into this trial immediately after failure of previous chemotherapy with 5-FU and cisplatin. The median time to progression was 4.3 months and the median overall survival was 7.3 months. The most common hematologic toxicity was grade 1-2 anemia in 39 cycles (39%). No grade 4 leukopenia or thrombocytopenia were observed. The most common non-hematologic toxicity was nausea/vomiting (33%). Peripheral neuropathy of grade 1 or 2 was noted (27%), but there was no grade 3 or 4 neurotoxicity. CONCLUSIONS: This phase II study of oxaliplatin, 5-FU and LV continuous infusion showed activity in previously platinum-treated patients with advanced gastric cancer, with acceptable toxicities.     

吉西他滨单药治疗老年晚期癌症

目的：观察吉西他滨(健择)单药治疗老年晚期癌症的疗效、临床受益反应(CBR)及毒性反应。方法：54例Ⅲ／Ⅳ期老年癌症患者采用吉西他滨1000mg/m^2，第1、8、15天静滴，每28天为一周期。按WHO标准评估疗效和毒副作用，同时综合评估CBR指标。结果：32例非小细胞肺癌有效率为21．88％，54例中CBR率90．7％，毒副反应很轻，对高龄患者也能耐受。结论：采用吉西他滨单药治疗疗效确切、低毒、安全，可作为老年晚期癌症患者的一线治疗方案。     

A phase II study of raltitrexed and gemcitabine in patients with advanced pancreatic carcinoma

Advanced adenocarcinoma of the pancreas has a very poor prognosis. The aim of this study was to assess the efficacy and tolerability of a combination of the chemotherapeutic agents gemcitabine and raltitrexed. Chemonaive patients with advanced adenocarcinoma of the pancreas were treated with a combination of raltitrexed (3.5 mg m(-2) on day 1 of a 21-day treatment cycle) and gemcitabine (800 mg m(-2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle). Between April 2000 and February 2003, 27 patients were enrolled onto the study. The mean duration of treatment was 11 weeks. Four of 27 patients experienced at least one episode of grade 3 or 4 neutropenia. One patient with grade 4 neutropenia died due to sepsis. Four of 27 patients experienced grade 4 diarrhoea. There was one partial remission (4%) and 12 patients experienced disease stabilisation (44%). The 6-month and 1-year survival rates were 37 and 11%, respectively. Symptomatic benefit occurred in seven (26%) patients. We conclude that a combination of raltitrexed and gemcitabine, using the schedule and doses in this study, cannot be recommended for patients with advanced pancreatic cancer.     

吉西他滨联合氟尿嘧啶和顺铂治疗晚期胰腺癌

目的：观察吉西他滨（CEM）,氟尿嘧啶（5－FU）及顺铂（DDP）三药联合化疗对晚期胰腺癌的客观疗效及其临床受益反应（CBR）,方法：GEM 800mg/m^2,5-FU 600mg/m^2,DDP 30mg/m^2,于第1,8,15天静滴,28天为1周期,按WHO标准评价疗效,同时综合评估临床受益反应（CBR）指标：疼痛,体力状况及体重变化。结果：全组共29例,25例化疗两周期以上,其中PR6例（24．0％）,NC12例（48．0％）,PC7例（28．0％）,参照CBR综合指标,CBR率为62．1％（18／29）,主要毒性为消化道反应及骨髓抑制,其中血小板Ⅲ-Ⅳ度毒性为27．6％（18／29）,失访18例,结论：吉西他滨联合氟尿嘧啶及顺铂对晚期胰腺癌具有一定的肿瘤客观解率,临床受益反应率高,毒副反应能耐受,值得进一步研究。     

Gemcitabine and oxaliplatin for metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II study.

BACKGROUND: This study was performed to determine the efficacy of gemcitabine and oxaliplatin in patients with advanced or metastatic pancreatic adenocarcinoma (ACA). PATIENTS AND METHODS: Pancreatic ACA patients with previously untreated advanced or metastatic disease were enrolled in a phase II study of gemcitabine and oxaliplatin. Oxaliplatin was given i.v. on day 1 and gemcitabine i.v. on days 1 and 8 of a 3-week cycle. The primary end point of the trial was 6-month survival. Secondary end points included response rate, overall survival, median time to progression and toxicity. RESULTS: A total of 47 patients were enrolled, 46 of whom were evaluable. Of those patients assessed for the primary end point 50% lived for > or =6 months. The median time to progression was 4.53 months. Five confirmed responses were seen with a median duration of response of 2.7 months. Overall, the treatment was well tolerated. However, one patient died as a result of treatment-related hemolytic uremic syndrome. CONCLUSIONS: Gemcitabine and oxaliplatin, at doses of 1000 mg/m(2) and 100 mg/m(2), respectively, showed moderate activity in patients with pancreatic ACA. Based on the results of this study further evaluation of this combination is warranted.     

Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study

Gemcitabine and oxaliplatin (GEMOX) are active as first-line therapy against advanced pancreatic cancer. This study aims to evaluate the activity and tolerability of this combination in patients refractory to standard gemcitabine (GEM). A total of 33 patients (median age of 57) were included with locally advanced and metastatic evaluable diseases, who had progressed during or following GEM therapy. The GEMOX regimen consisted of 1000 mg m(-2) of GEM at a 100-min infusion on day 1, followed on day 2 by 100 mg m(-2) of oxaliplatin at a 2-h infusion; a cycle that was given every 2 weeks. All patients received at least one cycle of GEMOX (median 5; range 1-29). Response by 31 evaluable patients was as follows: PR: 7/31(22.6%), s.d. > or = 8 weeks: 11/31(35.5%), s.d. < 8 weeks: 1/31(3.2%), PD: 12/31(38.7%). Median duration of response and TTP were 4.5 and 4.2 months, respectively. Median survival was 6 months (range 0.5-21). Clinical benefit response was observed in 17/31 patients (54.8%). Grade III/IV non-neurologic toxicities occurred in 12/33 patients (36.3%), and grade I, II, and III neuropathy in 17(51%), 3(9%), and 4(12%) patients, respectively. GEMOX is a well-tolerated, active regimen that may provide a benefit to patients with advanced pancreatic cancer after progression following standard gemcitabine treatment.     

Gemcitabine concurrent with continuous infusional 5-fluorouracil in advanced biliary cancers: a review of the Princess Margaret Hospital experience.

BACKGROUND: Unresectable biliary tract cancer has a very poor prognosis. A combination of weekly gemcitabine plus continuous infusional 5-fluorouracil (5-FU) (GEM/CVI 5-FU) was evaluated as therapy for this cancer. PATIENTS AND METHODS: The charts of 27 patients with advanced biliary tract adenocarcinoma treated with GEM/CVI 5-FU at the Princess Margaret Hospital were evaluated for response, survival and toxicity. The treatment consisted of a 30-min infusion of gemcitabine at 900 mg/m(2) on days 1, 8 and 15 of a 28-day cycle plus 5-FU given via a peripherally inserted central line at 200 mg/m(2)/day continuously for 21 days, every 28 days. RESULTS: Objective responses were observed in nine patients (33%; 95% confidence interval 17% to 54%). An additional eight patients (30%) achieved stable disease for a median of 4 months (range 2.3-11). Median time to progression and overall survival were 3.7 and 5.3 months, respectively. Direct chemotherapy-related toxicity was mild, with only 11% grade > or =3 myelosuppression. Central venous catheter complications were common (26%). There were no treatment-related deaths. CONCLUSIONS: This study shows that GEM/CVI 5-FU is active and well tolerated in advanced and metastatic biliary tract cancers.     

High-dose radiation therapy and neoadjuvant plus concomitant chemotherapy with 5-fluorouracil and cisplatin in patients with locally advanced squamous-cell anal canal cancer: Final results of a phase II study

Purpose:to analyse toxicity and response to a new scheme ofneoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT–CT)for locally advanced anal canal squamous-cell carcinoma (ACC). Patients and methods:Eighty patients with an ACC >40 mm and/orwith lymph node involvement were included (1 T₁, 52 T₂,14 T₃, 13 T₄, 18 N₀, 30 N₁, 32N₂–N₃). Two cycles of 5-fluorouracil (5-FU) andCDDP were delivered as neoadjuvant CT and two during RT–CT. Pelvic(± inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involvedfields were boosted after a one to two month gap (15–20 Gy). The medianfollow-up was 29 months. Results:One patient died of a pulmonary embolism on day 4. Allpatients received the entire treatment, with reduced 5-FU doses in 27%of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4toxicities were observed. No toxic death occurred.Complete response (CR) and partial response (PR) rates were, respectively,10% and 51% after neoadjuvant CT, 67% and 28%after RT–CT and 93% and 5% after treatment completion(including 4 abdomino-perineal resections).The three-year actuarial overall, tumour-specific, colostomy-free,relapse-free, disease-free and event-free survivals were 86%,88%, 73%, 70%, 67% and 63%,respectively. Conclusions:Tolerance was good. After neoadjuvant CT, most of thepatients were objective responders. After treatment completion, all but fiveachieved CR. The long-term results confirm the durability of local control andlow toxicity on the sphincter. An ongoing phase III intergroup trial analysesthe impact of neoadjuvant CT, and the benefit of a high-dose boostirradiation, on local control and colostomy-free survival.     

Clinical benefit response of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer

Background Pancreatic cancer is a highly virulent disease with a poor prognosis. Although objective tumor response to chemotherapy and/or radiotherapy is low, some patients show an improvement in their symptoms after treatments, without obvious tumor regression. Methods We assessed the clinical benefit of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer. Sixteen patients were enrolled in this study. The clinical benefit response to the chemoradiotherapy was evaluated by 2 indicators, including pain (intensity of pain and consumption of morphine) and performance status. A patient was defined to be a clinical benefit responder if 1 of these 2 variables was positive, and the other variable was positive or stable. Results Seven patients (44%) responded. Six patients (38%) were classified as stable, and 3 (19%) as nonresponders. The survival period in responders was significantly longer than that in nonresponders and stable patients. Conclusion Concurrent external-beam radiation therapy, with protracted 5-fluorouracil infusion, may be a meaningful treatment for locally advanced pancreatic cancer.