Adjuvant radiotherapy and concomitant 5-fluorouracil by protracted venous infusion for resected pancreatic cancer

Purpose: To assess the toxicity and clinical benefit from adjuvant chemoradiotherapy consisting of protracted venous infusion 5-fluorouracil (5-FU) and concomitant radiotherapy in patients with resected pancreatic cancer.

Methods and Materials: Between 1994 and 1999, 52 patients who underwent pancreaticoduodenectomy received adjuvant chemoradiotherapy. The tumor bed and regional nodes received a dose of 45 Gy in fractions of 1.8 Gy followed by boost to the tumor bed if the surgical margins were involved (total dose, 54 Gy). The patients also received concomitant 5-FU by protracted venous infusion (200–250 mg/m²/day, 7 days/week) during the entire radiotherapy course.

Results: Fifty-two patients (30 men, 22 women) were enrolled and treated on this protocol. The median age was 63 years (range, 38–78 years), and the median Karnofsky Performance Status was 80 (range, 70–100). Thirty-five percent had involved surgical margins and 59% had involved lymph nodes. All patients completed therapy, and there were no Grade IV/V toxicities observed. With median follow-up of 24 months (range, 3–52 months) for surviving patients, the median survival is 32 months, and 2-year and 3-year survivals are 62%, and 39%, respectively.

Conclusion: Radiotherapy with concomitant 5-FU by protracted venous infusion as adjuvant treatment for resected pancreatic cancer is well tolerated. This approach allows for greater dose intensity with reduced toxicity. The median survival of this cohort of patients compares favorably with our earlier experience and other published series.     

Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer

PURPOSE: The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer. METHODS: Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m(2)/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups. RESULTS: The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p = 0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p < 0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p < 0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months. CONCLUSIONS: EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer.     

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer

RATIONALE: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. METHODS AND MATERIALS: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). RESULTS: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). CONCLUSION: The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.     

Protracted infusional 5-fluorouracil (5-FU) with bolus mitomycin in 5-FU-resistant colorectal cancer

Background:MF (protracted infusion 5-fluorouracil (5-FU), 300mg/m²/24 hours plus bolus mitomycin, 7 mg/m² every 6weeks, maximum 4 doses), was recently shown in a randomised trial to besuperior to protracted 5-FU alone, as first-line chemotherapy for metastaticcolorectal cancer (Ross et al. Ann Oncol 1997; 8: 995–1001 [5]). We haveexamined the same regimen in patients with 5-FU-resistant disease. Patients and methods:MF was given to 24 patients with metastaticcolorectal cancer, median age 63 years. Two had progressed within four monthsof adjuvant 5-FU; the rest had already received palliative 5-FU, withprogression during (11 patients), within four months (5 patients) or afterfour months of completion (6 patients). The prior 5-FU regimens were bolus5-FU/FA (8 patients); 48 hour bolus + infusion 5-FU/FA (18 patients) orprotracted 5-FU alone (3 patients). Five patients had received more than oneprior 5-FU regimen. Results:Three patients, 12.5%, achieved WHO partialresponse; seven others had minor response or stable disease (SD or better =42%, 95% confidence interval (95% CI):22%–64%). Median failure-free survival (FFS) was 15 weeks;median overall survival was 9.0 months. No grade 3 or 4 drug toxicityoccurred, but dose reduction and/or interruption for persistent grade 2toxicity was required in eight patients (33%). Three patients(12.5%) had venous line problems (2 thrombosis; 1 dislodged). Therewere no toxic deaths. 12 patients (50%) went on to receive third-linetherapy after MF, including irinotecan or oxaliplatin. Conclusions:MF is a low-cost, well-tolerated regimen insecond-line treatment of metastatic colorectal cancer. The response rate andFFS obtained in this small group are similar to those reported for singleagent irinotecan. Half our patients obtained a useful period of control withMF before moving on to further treatment with new agents such as irinotecanand oxaliplatin.     

Protracted venous infusion 5-fluorouracil and interferon-{alpha} in advanced and refractory colorectal cancer

BACKGROUND: The management of patients with advanced colorectal cancer remainsdependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced5-FU activity can be achieved by either adding a modulator orby altering the administration schedule, in particular usinga protracted venous infusion. Based on encouraging phase IIdata using bolus 5-FU and interferon-     

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.     

Phase II study of continuous venous infusion of 5-fluorouracil in advanced pancreatic cancer

Continuous venous infusion of 5-fluorouracil (5FU) was investigated in 18 patients with measureable advanced cancer of the pancreas. 5FU was given for 7 days in a dose of 500 mg/m2 by continuous venous infusion over a 24-hour period and then followed by a dose of 170 mg/m2 for more than 28 days. Ten patients had no change including 1 patient with minor response, and 4 patients had disease progression. Serum CA19-9 levels were measured serially after chemotherapy in 13 of 14 evaluable patients. In 3 of 10 patients who showed high levels before treatment, serum CA19-9 levels were significantly decreasing after treatment.     

A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer

PURPOSE: The aim of this study was to evaluate the efficacy and tolerance of preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil (5-FU) in patients with resectable rectal cancer. METHODS AND MATERIALS: Patients with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group performance status <2 were included. CPT-11 (50 mg/m(2) weekly) and 5-FU (225 mg/m(2)/day continuous infusion, 5 days/week) were concurrently administered with radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. RESULTS: A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7). Planned treatment was delivered to most patients (median relative dose intensity for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3) were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement after CRT. CONCLUSIONS: This preoperative CRT schedule has been shown to be effective and feasible in a large population of patients with resectable rectal cancer.     

High-dose intraoperative radiotherapy for unresectable pancreatic cancer

PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.     

卡培他滨联合适形放疗对不能手术的老年胃癌患者的治疗效果

目的：探讨卡培他滨联合三维适形放疗（three-dimensionalconformalradiotherapy,3DCRT）治疗不能手术的老年胃癌患者的疗效。方法：从2007年1月至2009年l0月,32例不能手术切除、年龄超过65岁的老年胃癌患者,卡培他滨片1250 mg/m2,每天两次,1-14天,21天重复;同时联合3DCRT,处方剂量45Gy,1.8Gy/次,5次/周。用Kaplan-Meier法分析患者的生存率。结果：10例患者获得完全缓解（31.3%）,15例患者部分缓解（46.9%）;17例出现症状的患者中15例患者症状缓解（88.2%）。中位生存期为11.4个月。治疗过程中的不良反应可以接受。结论：卡培他滨联合3DCRT对不能手术的年龄大于65岁的老年患者有较好的治疗效果。     

卡培他滨联合适形放疗对不能手术的老年胃癌患者的治疗效果

目的:探讨卡培他滨联合三维适形放疗(three-dimensionalconformalradiotherapy,3DCRT)治疗不能手术的老年胃癌患者的疗效。方法:从2007年1月至2009年l0月,32例不能手术切除、年龄超过65岁的老年胃癌患者,卡培他滨片1250 mg/m2,每天两次,1-14天,21天重复;同时联合3DCRT,处方剂量45Gy,1.8Gy/次,5次/周。用Kaplan-Meier法分析患者的生存率。结果:10例患者获得完全缓解(31.3%),15例患者部分缓解(46.9%);17例出现症状的患者中15例患者症状缓解(88.2%)。中位生存期为11.4个月。治疗过程中的不良反应可以接受。结论:卡培他滨联合3DCRT对不能手术的年龄大于65岁的老年患者有较好的治疗效果。     

Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer.

From January 31, 1986 to January 31, 1989, 184 eligible patients were enrolled in a randomized study of either infusional or bolus 5-fluorouracil (5-FU) for the treatment of metastatic measurable colorectal cancer. Infusion was administered at an escalated dose schedule starting at 350 mg/m2 per day for 2 weeks with a 2-week rest period on a monthly basis, while bolus 5-FU was started at 400-450 mg/m2 for 5 days every 28 days. In these chemotherapy-naive patients with good performance status, the infusion arm produced a response in 11 of 88 patients versus 6 of 82 in the bolus arm (p = 0.384). Progression free survival was significantly longer (p = 0.0139) in the infusion group (3.8 versus 2.3 months), but no significant difference in survival was observed (p = 0.207). As expected, the toxicities of the regimens were different in character, but each had approximately a 20% incidence of significant toxicities. Neither of these methods of administering fluorouracil results in an exceptional response rate, nor does the infusion have an impact on survival as compared to the bolus route. If this type of complicated infusional approach is to continue, especially with increasing dosage (which could be accomplished on our schedule), randomized studies with survival as an endpoint must remain the gold standard.     

Continuous hepatic arterial infusion of 5-fluorouracil with leucovorin for unresectable liver metastases from colorectal cancer

Twenty-three patients with liver metastases from colorectal cancer were treated by continuous hepatic arterial infusion chemotherapy with 5-FU and Leucovorin. The regimen was that 500 mg/body of 5-FU with 30 mg/body of Leucovorin was administered continuously for 5 days, followed by no medication for 16 days. The effect of this therapy was evaluated and the relationship between this therapy and the overexpression of vascular endothelial growth factor (VEGF) or microvessel density (MVD) was also studied. Complete response was obtained in 4 patients and partial response in 3 patients; the response rate was 32%. The response rate was 60% in patients who underwent more than 7 courses. The response rate was 44% in patients with positive VEGF and 33% in patients with negative VEGF. The response rate was 50% in patients with an MVD of more than 30 and 33% in patients with an MVD of less than 30. The 3-year survival rate for patients who underwent more than 7 courses was 37.5%. This therapy had to be abandoned in 6 patients due to occlusion of the catheter. Skillful maintenance of the catheter is necessary for a high response rate and satisfactory prognosis using this therapy.     

A pilot study of protracted venous infusion of 5-fluorouracil and concomitant radiation therapy

A method to potentially increase the effectiveness of combination 5-fluorouracil (5-FU) and radiation therapy (XRT) using protracted (more than 30 days) venous infusion (PVI) of 5-FU with conventionally fractionated XRT (180 to 200 cGy per day) (100 cGy = 100 rad) is described. Forty-one patients were treated with this combination with acceptable acute toxicity. In 95% of patients, the toxicity was mild or moderate and symptom control was achieved with medications or a short treatment interruption. In two patients (5%), severe gastrointestinal side effects resulted in cessation of all therapy. This method of administration of 5-FU is feasible, and we have demonstrated that it can be safely used with a course of conventionally fractionated, high-dose (approximately to 6,500 cGy) radiation therapy.     

5-氟尿嘧啶缓释剂植入治疗局部进展期胰腺癌

目的 探讨5-氟尿嘧啶(5-Fu)缓释剂植入治疗局部进展期胰腺癌的效果和安全性.方法 将85例局部进展期胰腺癌患者随机分为两组:试验组50例,行术中5-Fu缓释剂植入;对照组35例,仅行术中穿刺组织细胞学诊断,加或不加内引流术.观察客观疗效、临床受益反应、不良反应、并发症及生存情况.结果 试验组部分缓解6例,稳定32例,进展12例,临床受益率为52.0%.无明显毒性反应,2例发生胰瘘,均经保守治疗治愈.试验组和对照组中位生存时间分别为9.0和4.0个月,6个月生存率分别为56.8%和31.4%,12个月生存率分别为22.9%和2.9%,两组生存率差异有统计学意义(P=0.012).结论 5-Fu缓释剂植入治疗局部进展期胰腺癌有一定疗效,能延长患者生存时间,提高患者生活质量,无明显毒副作用,是一种安全有效的治疗方法.     

适形放射治疗联合热疗治疗晚期胰腺癌的疗效及临床受益反应观察

为了评价适形放疗联合热疗治疗晚期胰腺癌的疗效及临床受益反应,对34例胰腺癌患者给予适形放疗,2Gy/次,5次/周,总剂量50-70 Gy;热疗2次/周,每次60-90 min,共计6次。结果82.4%患者胸背部疼痛明显缓解,临床受益反应有效率91.2%;放疗后2个月复查CT,肿瘤缩小〉25%者76.5%;1、2年生存率分别为38.2%和20.6%。初步研究结果提示,适形放射治疗联合热疗治疗晚期胰腺癌,疗效较好,并发症少,可显著提高患者生活质量,是不能手术患者较好的治疗方式。     

Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer

PURPOSE: Full-dose gemcitabine and concurrent radiotherapy is a promising treatment approach in unresectable pancreatic cancer. This study was conducted to assess the pattern of failure and toxicity associated with the use of conformal treatment volumes, omitting prophylactic lymph node irradiation. METHODS AND MATERIALS: Seventy-four patients with locally advanced pancreatic cancer were treated between 1997 and 2005 with full-dose (1000 mg/m(2), Days 1, 8, and 15) gemcitabine and concurrent radiotherapy (36 Gy [median] in 15 daily fractions). The planning target volume (PTV) was limited to the gross tumor volume (GTV) plus 1-cm margin. Patient computed tomography (CT) scans were systematically reviewed to determine the pattern of failure. Kaplan-Meier and Cox-regression models were used to analyze freedom from local progression (FFLP), distant failure, overall survival (OS), and toxicity. RESULTS: With a median follow-up of 10.6 months (20.6 months in living patients), the 1-year and 2-year FFLP rates were 64% and 38%, respectively. Four patients (5%) failed in the peripancreatic lymph nodes (3 in-field and 1 marginal failure). Median OS was 11.2 months. Analyzed as a time-dependent covariate, local failure was a significant predictor of OS (p = 0.0074). Sixteen patients (22%) had significant gastrointestinal (GI) toxicity (> or = Grade 3). PTV correlated with significant GI toxicity (p = 0.007). CONCLUSIONS: Freedom from local progression in unresectable pancreatic cancer is suboptimal. In conjunction with full-dose gemcitabine, the use of conformal fields encompassing only the GTV helps reduce toxicity and does not result in marginal failures. Our findings provide rationale for intensification of local therapy in conjunction with more effective systemic therapy.     

A phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable biliary tract cancer

Background

Many clinical trials have been conducted with gemcitabine- or 5-fluorouracil-based regimens as treatment for unresectable biliary tract cancer; however, the results remain unsatisfactory. Because further therapeutic improvements are required, we conducted a phase I study of arterial infusion chemotherapy using a combination of gemcitabine and 5-fluorouracil.

Methods

In the first 3 cohorts, patients were to receive an arterial infusion of gemcitabine 600, 800 or 1000?mg/m², respectively, over 30?min on days 1 and 15, plus a continuous arterial infusion of 5-fluorouracil 300?mg/m²/day on days 1–5 and 15–19. In the final cohort, patients were to receive an arterial infusion of gemcitabine 1000?mg/m² over 30?min on days 1 and 15, plus 5-fluorouracil 400?mg/m²/day on days 1–5 and 15–19.

Results

Eighteen patients were enrolled. In the final cohort, three of six patients experienced grade 3 non-hematological toxicities (cholecystitis, cellulitis and pneumonia). Thus, we determined the maximum tolerated doses of gemcitabine and 5-fluorouracil in arterial infusion chemotherapy to be 1000 and 400?mg/m², respectively.

Conclusion

This regimen of gemcitabine and 5-fluorouracil is tolerable and warrants further investigation in biliary tract cancer.     

Protracted venous infusion 5-fluorouracil in combination with subcutaneous interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer: a phase II study

Our purpose was to assess the activity of alpha-interferon (IFN-alpha), interleukin-2 (IL-2) and 5 fluorouracil (5FU) administered by protracted venous infusion (PVI) as opposed to bolus injection. 55 patients with advanced renal cell cancer were treated as follows: IL-2 and IFN-alpha according to the schedule originally described by Atzpodien, with PVI 5FU 200 mg m(-2)day(-1)during weeks 5-9. 42 patients (76%) were of moderate or poor prognosis as defined by previous studies. The response rate by intention to treat was 31% (17 of 55, three complete response, 14 partial response; 95% CI = 19-45%) and in evaluable patients (completed one cycle, n = 42), it was 40% (95% CI = 26-57%). In addition, 24% (13 of 55) patients achieved disease stabilization. The overall median survival was 11 months with a 1-year survival of 45%. The median survival for evaluable patients was 18 months with 1- and 2-year survivals of 60% and 40% respectively. The median survival of responding patients was 31 months and the three patients achieving complete response remain progression-free at 14+, 18+ and 23+ months. Evaluable patients with poor prognostic features achieved a response rate of 54% and median survival of 18 months. Toxicity was significant yet manageable with 12 patients unable to complete one cycle due to side-effects and 36% experiencing grade 3-4 toxicities. The three on-treatment deaths were considered unlikely to be due to toxicity. The schedule of IFN-alpha, IL-2 and PVI 5FU has significant activity in advanced renal cell cancer with manageable toxicity. It is of particular interest that this regimen appears to have high activity in fit patients with poor prognostic features.