Bolus 5-fluorouracil Research Articles

Commentary: practice patterns and potential impact on quality measures for a practicing physician.

Commentary: practice patterns and potential impact on quality measures for a practicing physician.

Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients

BackgroundCombination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.MethodsWe prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged ≥ 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups.ResultsThe main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (≥ grade 3) and 87.5% (≥ grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference.ConclusionmFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.

Is there a palliative benefit of gemcitabine plus fluoropyrimidines in patients with refractory colorectal cancer? A review of the literature

Introduction: Fluoropyrimidines with oxaliplatin or irinotecan plus bevacizumab is the standard chemotherapy combination in patients with advanced colorectal cancer (CRC). Gemcitabine acts synergistically with fluoropyrimidines to enhance the binding of thymidylate synthase and increase inhibition of DNA synthesis. The objective of this review is to evaluate the literature for evidence of efficacy and safety of fluoropyrimidine plus gemcitabine (FG) in patients with advanced CRC. Methods: Relevant studies were identified in PubMed, Ovid, Cochrane database and the American Society of Clinical Oncology abstracts using the following search terms: gemcitabine, fluorouracil, capecitabine and colorectal cancer. Only studies using the FG combination were selected. Results: Forty-two advanced CRC patients were evaluated in two Phase I studies and the maximum tolerated dose of gemcitabine was 900 – 1,000 mg/m2 weekly with either bolus 5-fluorouracil (5-FU) or capecitabine. A total of 216 advanced CRC patients were evaluated in six Phase II studies. Gemcitabine (750 – 1,250 mg/m2) with either 5-FU (continuous infusion or bolus) or capecitabine was administered as first-line therapy in two studies and as third-line therapy in three studies. The range reported for overall response rate was 30 – 38.3%, median time to progression was 4 – 8.3+ months and median survival was 9.8 – 18+ months. The most commonly reported grade 3 – 4 toxicities were neutropenia, thrombocytopenia and mucositis. Conclusions: Fluoropyrimidine plus gemcitabine is clinically active in patients with refractory CRC demonstrating prolonged median time to progression and acceptable toxicity only when bolus 5-FU was not used. Studies are underway to evaluate the combinations of FG with other chemotherapy or targeted agents. Meanwhile, FG may be considered for patients with advanced CRC who are refractory to primary treatment without other options or who are not eligible for clinical studies.

Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment.

The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

Second-line chemotherapy with FOLFIRI in patients with metastatic gastric cancer (MGC) not previously treated with fluoropyrimidines

4549 Background: No established second-line chemotherapy exists for patients (pts) with MGC failing to respond or progressing after first-line chemotherapy. This study was designed to determine the efficacy and safety of FOLFIRI combination used as second-line therapy in pts with MGC not previously treated with regimens containing fluoropyrimidines. Methods: Pts with measurable distant metastases, previously treated with a combination of epirubicin, docetaxel and cisplatin or oxaliplatin as first-line therapy, received irinotecan 180 mg/mq (150 mg/mq in pts &gt;70 ys old) as a 1-h infusion day 1; leucovorin 100 mg/mq/day followed by bolus fluorouracil (FU) 400 mg/mq and a 22-h infusion of FU 600 mg/mq day 1–2, every 2 weeks for a maximum of 12 cycles or until disease progression, unacceptable toxicity or patients refusal. Endpoints were response rate (RR), time to progression (TTP), overall survival (OS) and safety. Results: 38 pts were enrolled: M/F 23/15; median age 66 ys (34–75); median ECOG PS 1 (0–2); number of metastatic sites 1/2/≥3: 9/18/11 pts, respectively. A total of 223 cycles was performed (median 6, range 2–12). One CR and 8 PR were observed for an overall RR of 24% (95% CI, 11–39 %). Disease remained stable in 11 pts. Median TTP was 4.0 months (95% CI, 2.9–5.1) and median OS was 6.2 months (95% CI, 4.7–7.7). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 29%, 3% and 8% of pts, respectively. Febrile neutropenia was seen in 2 pts (5%). Other grade 3 toxicities included diarrhea in 5 pts (13%), mucositis in 2 pts (5%) and vomiting in 2 pts (5%). There were no treatment related deaths. Conclusions: FOLFIRI is an active and well tolerated second-line regimen for MGC pts not previously treated with fluoropyrimidines. No significant financial relationships to disclose.

Postoperative LV5FU2 combination chemotherapy in patients with curative resected advanced gastric cancer

e15660 Background: To illuminate the effect and toxicity of fortnightly low-dose leucovorin(LV) and fluorouracil(5FU) bolus plus continuous infusion(LV5FU2) postoperative chemotherapy(adjuvant) in patients with curative resected, advanced gastric cancer. Methods: Total 40 patients were enrolled in this study. All patients received LV 20mg/m2(bolus), 5FU 400mg/m2(bolus), 5FU 600mg/m2(24-hour continuous infusion) on day 1, 2, 15, and 16, every 4 weeks(LV5FU2), total 6 cycles. Results: Postoperative chemotherapy was initiated median 19 days after surgery. Total of 238 cycles were administered and median follow-up was 602 days. The median disease-free survival time was 728 days (95% CI, 411∼1045) and 2-year overall survival was 77%. Relapses were reported in 18 (45%) of the patients : Two of 9 patients relapsed in stage IIIA (22.2%), seven of 12 patients relapsed in stage IIIB (58.3%) and nine of 17 patients relapsed in stage IV (52.9%). They were all distant relapsed. Eight patients died. 7 patients died as a result of cancer progression and 1 patient suicided while receiving palliative chemotheraphy for cancer relapse. The grade 3∼4 toxicity of neutropenia 8.4% and anemia 0.4%, neutropenic fever 0.4% were observed. Conclusions: Postoperative LV5FU2 adjuvant chemotherapy is effective and tolerable for the patients with curative resected, advanced gastric cancer. No significant financial relationships to disclose.

Preoperative concomitant chemoradiotherapy with oxaliplatin and 5-fluorouracil in locally advanced rectal carcinoma

e15108 Background: Preoperative concomitant chemoradiotherapy has shown to improve local control and sphincter preservation with decreased acute toxicity compared with postoperative treatment in locally advanced rectal carcinoma. The primary endpoint of this phase II trial was pathologic tumor response. Secondary endpoint was sphincter preservation and toxicity Methods: Inclusion criteria: rectal adenocarcinoma &lt;12 cms from anal verge, clinical stage T3–4, adequate renal, hematological and liver function. Planned sample for this trial was 40 patients. Treatment schedule: Pelvic radiotherapy (25 Gy/ 5 fractions: 5 Gy on day 1 to day 5) and chemotherapy: Oxaliplatin 85 mg/m2 on 2 hours, day 1 and 15, folinic acid 20 mg/m2 and 5 fluoro-uracil bolus 500 mg/m2 on day 1, 8 and 15 (cycle repeated every 4 weeks). Surgery with TME was performed after the end of the second cycle of chemotherapy. Adjuvant chemotherapy with 5FULV2 was administered after surgery Results: 15 patients have been recruited between January and October 2006: 10 males/5 females. Median age: 45 years (range 26–62). Clinical stage (determined by CT or RMI): T3: 66.6% and T4: 33.3%. Tumor location (from anal verge): &lt; 6 cm in 10pts, &gt;6 cm in 5pts. Surgery (performed in 14 patients) consisted of low anterior resection in 5pts and abdominal-perineal resection in 10p. Tumor down-staging was observed in 10pts (66.6%), including 5pts with complete pathological response (33.3%). Main adverse effects (NCI-CTC): diarrhea G3–4: 14.2%, sensitive peripheral neurotoxicity G1: 26.6%, nausea/vomiting G3–4: 11%, Anemia G3–4: 7.1%, neutropenia G3–4: 14.2% Conclusions: Preliminary results show that preoperative concomitant chemoradiotherapy with oxaliplatin and 5FU-folinic acid is an effective regimen with an acceptable safety profile for locally advanced rectal cancer, leading to a high probability of tumor downstaging. This interim analysis has to be confirmed by the final analysis. No significant financial relationships to disclose.

P27Kip1 in stage III colon cancer: implications for outcome following adjuvant chemotherapy in cancer and leukemia group B protocol 89803.

In retrospective studies, loss of p27(Kip1) (p27), a cyclin-dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for stage III colon cancer. Cancer and Leukemia Group B protocol 89803 randomized 1,264 stage III colon cancer patients to receive weekly bolus 5-fluorouracil/leucovorin or weekly bolus irinotecan, 5-fluorouracil, and leucovorin (IFL). The primary endpoint was overall survival (OS); disease-free survival was a secondary endpoint. Expression of p27 and DNA mismatch repair proteins were determined by immunohistochemistry in primary tumor and normal tissue from paraffin blocks. Data were analyzed using log-rank test. Of 601 tumors analyzed, 207 (34.4%) showed p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27-negative tumors showed reduced OS [5-year OS 66%: 95% confidence interval (95% CI), 0.59-0.72 versus 75%: 95% CI, 0.70-0.79; log-rank P = 0.021]. This relationship was not influenced by treatment arm. Combination of p27 status with mismatch repair status, however, identified a small subset of patients that may benefit from IFL (n = 36; 5-year disease-free survival 81%: 95% CI, 0.64-0.98 versus 47%: 95% CI, 0.21-0.72; log-rank P = 0.042; 5-year OS 81%: 95% CI, 0.64-0.98 versus 60%: 95% CI, 0.35-0.85; log-rank P = 0.128). Loss of p27 is associated with reduced survival in stage III colon cancer but by itself does not indicate a significant difference in outcome between patients treated IFL or 5-fluorouracil/leucovorin.

Microsatellite Instability Predicts Improved Response to Adjuvant Therapy With Irinotecan, Fluorouracil, and Leucovorin in Stage III Colon Cancer: Cancer and Leukemia Group B Protocol 89803

Colon cancers exhibiting DNA mismatch repair (MMR) defects demonstrate distinct clinical and pathologic features, including better prognosis and reduced response to fluorouracil (FU) -based chemotherapy. This prospective study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient (MMR-D) colon cancers. Cancer and Leukemia Group B 89803 randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin (LV) or weekly bolus irinotecan, FU, and LV (IFL). The primary end point was overall survival; disease-free survival (DFS) was a secondary end point. Tumor expression of the MMR proteins, MLH1 and MSH2, was determined by immunohistochemistry (IHC). DNA microsatellite instability was also assessed using a panel of mono- and dinucleotide markers. Tumors with MMR defects were those demonstrating loss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype. Of 723 tumor cases examined by genotyping and IHC, 96 (13.3%) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases (97.1%). IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors (0.76; 95% CI, 0.64 to 0.88 v 0.59; 95% CI, 0.53 to 0.64; P = .03). This relationship was not observed among patients treated with FU/LV. A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV (0.57; 95% CI, 0.42 to 0.71 v 0.76; 95% CI, 0.64 to 0.88; P = .07; hazard ratio interaction between tumor status and treatment, 0.51; likelihood ratio P = .117). Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen as compared with those receiving FU/LV.

Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer: A pilot study

To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma. We initiated a regimen with at day 1 an injection (iv) of bevacizumab at 5 mg/kg, followed by 180 mg/m(2) irinotecan, followed by Leucovorin 400 mg/m(2), followed by a 5-Fluorouracil bolus 400 mg/m(2); and a 46-h infusion 2400 mg/m(2). Sirolimus was given orally as continuous administration of 2 mg twice a day every days. This treatment was repeated every 14 d. A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wild-type patients. The median number of cycles was 8.5 (range 2-20) and clinical benefit was observed in eight patients. The median time to progression was 5 mo and the median survival was 8 mo. Grade 3 neutropenia developed in four patients, and grade 3 diarrhea and stomatitis in two. The combination regimen of 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in advanced colorectal carcinoma after failure of classical treatment is feasible and promising. Further evaluation of this combination is required.

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m(2)/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m(2)/d. Continuous-infusion 5-FU at 225 mg/m(2)/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.

Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741.

In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups. A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase). Multivariate prognostic factor analysis was used to assess clinical factors for their relationships to OS, TTP, response, and toxicity by using Cox and logistic regression models. The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128). OS and TTP were significantly longer for FOLFOX (20.2 months and 8.9 months, respectively) than for IFL (14.6 months and 6.1 months, respectively; P < .001 for both) or for IROX (17.3 months and 6.7 months, respectively; P < .001 for both). OS differed by risk group: 20.7 months for low risk, 17.4 months for intermediate risk, and 9.4 months for high risk (P < .001). FOLFOX treatment was superior in all risk groups and was the most powerful prognostic factor for OS, TTP, response rate, and toxicity. The 9.8% 5-year OS in patients with metastatic colorectal cancer who were treated with first-line FOLFOX sets a new benchmark. Neither baseline risk group nor any prognostic factor examined was predictive of treatment-specific outcome. However, treatment efficacy and patient longevity varied as a function of risk group.

Modified irinotecan plus bolus 5-fluorouracil/L-leucovorin for metastatic colorectal cancer at a single institution in Japan

The modified irinotecan plus bolus 5-fluorouracil/L-leucovorin (IFL) regimen (irinotecan plus bolus 5-fluorouracil/L-leucovorin) used to be one of the standard treatments for metastatic colorectal cancer until approval of oxaliplatin in Japan. We evaluated the efficacy of modified IFL therapy for Japanese patients. Forty-seven patients with metastatic colorectal cancer received irinotecan (100 mg/m(2)) and bolus 5-fluorouracil (500 mg/m(2)) plus L-leucovorin (10 mg/m(2)) on days 1 and 8 every 3 weeks until progression or unmanageable toxicity occurred. The data on toxicity and tumor response were analyzed retrospectively. All patients discontinued modified IFL therapy due to cancer progression, except for one patient who developed severe liver dysfunction. The overall response rate was 25%. The median progression-free survival time (PFS) was 8.6 [corrected] months. The median overall survival time (OS) was 27.8 [corrected] months for all patients, 30.9 [corrected] months for patients receiving subsequent oxaliplatin therapy, and 14.5 [corrected] months for patients without oxaliplatin (P = 0.0031). According to multivariate analysis results, good performance status, a normal white cell count, and absence of local recurrence were associated with a better PFS. Tumor response was a good prognostic factor for both PFS and OS. Gastrointestinal symptoms were the most common toxicities, including grade 3 diarrhea (8%) and grade 3 anorexia (10%). Grade 4 neutropenia occurred in 6% of patients. No other drug-related severe adverse events or deaths were observed. Modified IFL therapy is an effective and well-tolerated regimen for Japanese patients with metastatic colorectal cancer. Modified IFL therapy combined with biological agents might remain an option for some patients who refuse a central venous catheter.

New Lessons From “Old” Chemotherapy in Colorectal Cancer

New Lessons From “Old” Chemotherapy in Colorectal Cancer

Adjuvant chemotherapy of colon cancer current strategies

Adjuvant chemotherapy has become a standard of care in patients with early stage colon cancer. 5-Fluorouracil modulated by leucovorin is the mainstay of treatment, but it has evolved from the bolus administration to continuous infusion and combination therapy. Oral fluoropyrimidines may be an alternative to bolus 5-fluorouracil plus folinic acid. The benefit of adjuvant therapy is established in stage III colon cancer, whereas in stage II the evidence supporting the adjuvant therapy is still poor. Current issues concern the duration of treatment, the development of new schedules and strategies including biological agents and the identification of prognostic and predictive biological markers.

Pancreatic Cancer – Low Survival Rates: Gemcitabine More Useful

From the point of view of the DKG-S3 Guideline Committee for Exocrine Pancreatic Carcinoma, the following points should be discussed which were neglected in the review of Beger et al.. In the paragraph on adjuvant chemotherapy (Cx), the authors imply that the 5-fluorouracil bolus protocol, as used in the ESPAC-1 study, is the standard adjuvant chemotherapy after R0-resection. However, the S3 guideline (3) recommends that the 5-fluorouracil bolus protocol should not be used. On the contrary, the guideline unambiguously recommends adjuvant Cx with gemcitabine, because disease-free survival and overall survival were improved by gencitabine in the CONK0-001 study (2). Even though it was expected that bolus 5-fluorouracil and gemcitabine would be equipotent in the ESPAC-III study, gemcitabine would still be preferable as Cx, as the tolerability is better and the handling simpler. The authors’ sentence Some data, however, demonstrate that adjuvant palliative chemoradiotherapy can improve the prognosis for the R1/R2 resected is likewise inconsistent with the S3 guideline. Based on the subgroup analysis of the CONK0-001 study, this advocates additive palliative Cx with gemcitabine. Although a metaanalysis (4) found a trend towards benefit with adjuvant radiochemotherapy in comparison with resection alone, there are no data comparing this with chemotherapy alone. Because of the markedly higher toxicity and stress to the patient in comparison to gemcitabine for what is usually palliative treatment, the guideline regards this procedure as only an option for the individual patient. The guideline recommends that radiochemotherapy after R1 resection should, if at all possible, be performed in the form of randomized controlled study protocols. We are urgently awaiting the results of prospective randomized studies to clarify this important question.

Distal Bowel Surgical Margin Shorter than 1 cm After Preoperative Radiation for Rectal Cancer: Is It Safe?

The primary end-point of our randomized trial was sphincter preservation. The secondary aim was to evaluate whether distal bowel clearance < or =1 cm is safe after radiation. The study randomized 312 patients with cT3-4 resectable low-lying and mid-rectal cancer to receive either preoperative irradiation (5 x 5 Gy) with immediate total mesorectal excision (TME) or chemoradiation (50.4 Gy, bolus 5-fluorouracil and leucovorin) with delayed TME. After anterior resection, pathologists prospectively measured macroscopic and microscopic distal bowel clearance. Macroscopic and microscopic distal bowel clearance, distal intramural spread, sphincter preservation, local control, disease-free survival, and overall survival did not differ in the two randomized groups. Pooled analysis of the two groups showed that the incidence of local recurrence at 4 years (median follow-up) for patients with macroscopic clearance < or =1 cm (n = 42) and >1 cm (n = 124) was 11.3% and 15.4%, respectively (P = 0.514); the hazard ratio (HR) was 0.70, and the 95% confidence interval (CI) was 0.23-2.07. The corresponding values for patients with microscopic clearance < or =1 cm (n = 51) and >1 cm (n = 101) were 9.6% and 17.6% (P = 0.220; HR 0.51; 95% CI 0.17-1.53). After preoperative radiotherapy, distal bowel clearance < or =1 cm did not compromise local control.

Survival from cancer of the pancreas in England and Wales up to 2001.

Survival from cancer of the pancreas in England and Wales up to 2001.

Epirubicin, taxotere and fluorouracil modulated by folinic acid in the treatment of advanced gastric cancer: A phase II study of the Gruppo Oncologico dell’ Italia Meridionale (GOIM)

IntroductionDespite the large number of drugs active in AGC, no combination can be considered as the gold standard treatment. Modest increase have been obtained in overall survival with the most widely employed regimens such as CF or ECF, often obtained at expense of increased toxicity. So there is a strong need to develop new active drugs to improve the clinical outcome. Taxotere showed to be effective in preclinical studies and some phase II trials confirmed its clinical efficacy. Recently, the addition of TXT to CDDP + FU (TCF regimen), obtained, in a large randomised phase III trial, better survival than CF alone. However the toxicity of this combination was relevant and mainly due to the association with CDDP. Considering these data the GOIM started a phase II study aiming to evaluate efficacy and safety of a three drugs combination, employing EPI instead of CDDP. Materials and methodsForty-one histologically proven untreated gastric cancer patients, with advanced measurable disease, age between 18 and 75 years, performance status ⩾70 (Kfsky scale) and available to sign written informed consent, were enrolled. They received the following treatment: Epirubicin at 60mg/m2 on day 1, Taxotere at 50mg/m2 on day 1, Folinic Acid at 100mg/m2 on days 1–2, Fluorouracil bolus at 400mg/m2 on days 1–2 and Fluorouracil 22h continuous infusion on days 1–2 every three weeks. ResultsAmongst the 38 evaluable patients we observed 5 CR (13%), 9 PR (24%), 9 SD (24%) and 15 PD (39%) for an ORR of 37% (95% CI: 22–52) and a tumor growth control rate of 61%. The median time to progression was 4 months and the median survival was 9 months.The treatment was well tolerated. The main grade III–IV haematologic toxicities were leucopenia 7%, neutropenia 5% and anemia 5% while non-haematologics were diarrhoea 2%, alopecia 2% and cardiac 2%. ConclusionThe three drugs combination of Taxotere, Epirubicin and Fluorouracil is active and well tolerated first-line treatment in advanced gastric cancer patients.

Treatment of advanced gastric carcinoma patients with calcium folinate, a 5-fluorouracil bolus and continous infusion with 5-fluorouracil combined with oxaliplatin

To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil (5-FU) bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin (L-HOP)in treating advanced gastric carcinoma patients. Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin. The effects of treatment and toxicity were observed. There were 4 complete responses, 26 partial responses, 30 with no change and 5 with progressive disease. The overall effective response rate was 46.2% (30/65). The median duration was 7 months, with the main side effects including nausea and vomiting, peripheral phlebitis, alopecia, leukopenia, dental ulcers, peripheral neuritis and diarrhea. All the side effects were tolerated and minimal. The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma. This therapeutic regimen is of value for these patients.