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Ca Στομάχου

Ca Στομάχου

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Ca Στομάχου

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  1. Ca Στομάχου Στέργιος Β. Μπούσιος Ογκολόγος - Παθολόγος Ογκολογική Κλινική Πανεπιστημιακό Γενικό Νοσοκομείο Ιωαννίνων Διευθυντής: Καθηγητής Νικόλαος Παυλίδης

  2. Patient • 68 yrs old • Operated stomach Ca • Stage: IIIb – TNM staging: T3N2 • D2 excision www.ioannimamed.gr

  3. Epidemiology • 5th highest incidence & 4th most common cause of cancer-related death • Increasing incidence of EGJ and gastric cardia tumors • Declining overall incidence • Peak incidence during the 7th decade • Twice as common in men compared to women • USA, 2010: 21,000 new cases – 10,570 deaths www.ioannimamed.gr

  4. Risk factors • Gender: Male • Smoking • Helicobacter pylori infection (mainly for adenocarcinoma) • Atrophic gastritis • Partial gastrectomy • Menetrier’s disease • Obesity (for OGJ/cardia tumors) • Genetic factors: familial adenomatouspolyposis, Peutz-Jeghers syndrome, hereditary non-polyposis colorectal cancer • Diet: red meat, smoked foods, spices, foods rich in hydrocarbons www.ioannimamed.gr

  5. TNM staging (1) • Primary tumor (T) • TX: primary tumor cannot be assessed • T0: no evidence of primary tumor • Tis: carcinoma in situ (intraepithelial tumor w/o invasion of the lamina propria) • T1: tumor invades lamina propria or submucosa • T2: tumor invades the muscularispropria (T2a) or the subserosa (T2b) • T3: tumor penetrates the serosa w/o invading adjacent structures • T4: tumors invades adjacent structures www.ioannimamed.gr

  6. TNM staging (2) • Regional lymph nodes (N) • NX: regional lymph nodes cannot be assessed • N0: no regional lymph nodes metastasis • N1: metastasis in 1-6 regional lymph nodes • N2: metastasis to 7-15 regional lymph nodes • N3: metastasis in more than 15 regional lymph nodes • Distant metastasis (M) • MX: distant metastasis cannot be assessed • M0: no distant metastasis • M1: distant metastasis www.ioannimamed.gr

  7. AJCC stage grouping • Stage 0: TisN0Mo • Stage IA: T1N0M0 • Stage IB: T1N1M0, T2aN0M0, T2bN0M0 • Stage II: T1N2M0, T2aN1M0, T2bN1M0, T3N0M0 • Stage IIIA: T2aN2M0, T2bN2M0, T3N1M0, T4N0M0 • Stage IIIB: T3N2M0 • Stage IV: T4N1M0,T4N2M0, T4N3M0, T1N3M0, T2N3M0, T3N3M0, anyTanyNM1 www.ioannimamed.gr

  8. Preoperative clinical staging • Endoscopic ultrasound (EUS): tumor invasion depth assessment • Computed tomography (CT) • Combined positron emission tomography (PET-CT): lower sensitivity than CT but improved specificity • Magnetic resonance imaging (MRI) • Laparoscopic staging www.ioannimamed.gr

  9. Principles of surgery • Primary treatment for early stage gastric cancer • Distal gastric cancer => subtotal gastrectomy • Proximal gastric cancer => proximal and total gastrectomy • For T1b – T3 => recommended subtotal or total gastrectomy • For T4 => en bloc resection of involved structures • Unresectable carcinomas: • Evidence of peritoneal involvement • Evidence of distant meatastases • Evidence of locally advanced disease www.ioannimamed.gr

  10. Lymph node dissection • D0 dissection: incomplete resection of N1 lymph nodes • D1 dissection: removal of the involved proximal or distal part of the stomach or of the entire stomach • D2 dissection: removal of the omental bursa and the front leaf of the transverse mesocolon – the corresponding arteries are cleared www.ioannimamed.gr

  11. EMR & laparoscopic resection • EMR • For early gastric cancer (Tis or T1a) • Well-differentiated histology • Tumors < 30mm • Ulceration absence • No evidence of invasive findings • Laparoscopic resection • Advantages: reduced blood loss and post-operative pain, accelerated recovery, early return to normal bowel function www.ioannimamed.gr

  12. Radiation • Adjuvant and neoadjuvant • BSCG trial: • No survival benefit due to post-operative RT or chemo • Reduced locoregional relapse with adjuvant RT • Review and meta-analysis: 5-year survival benefit with the addition of RT in patients with resectable gastric cancer • External-beam RT (45-50.4 Gy) does not improve survival in unresectable gastric cancer • EBRT concurrently with 5-fluorouracil improves survival www.ioannimamed.gr

  13. Combined modality treatment (1) • Preoperative chemoRT: 45Gy EBRT + 5-FU infusion followed by surgery and IORT (10Gy) in resectable gastric cancer • 83% underwent D2 lymphadenectomy • 63% significant pathologic response • 11% complete pathologic response • Preoperative induction chemo followed by chemoRT yields pathologic response resulting in improved survival www.ioannimamed.gr

  14. Combined modality treatment (2) • Postoperative chemoRT in patients with stomach adenocarcinoma or GE junction (stage IB – IV M0) • 5 monthly cycles of bolus chemo (5-FU & leucovorin) with RT (45Gy) concurrent with cycles 2 & 3 • Significant decrease in local failure compared with surgery only • Increase in median survival, 3 yrs RFS & OS compared with surgery only www.ioannimamed.gr

  15. Chemotherapy(1) • MAGIC trial (perioperative ECF chemo): • improved 5-year survival rates (36% compared to 23% for surgery only) • Improved PFS & OS in operable gastric and lower esophageal adenocarcinoma • North America trial (postoperative chemo): • 5 cycles of chemo (5-FU & leucovorin) before, during and after RT resulted in 15% 5-year OS improvement • Standard therapy in the USA, no standard acceptance in Europe (late toxicity & quantity of surgery) • Europeans consider postoperative chemoRT is beneficial after D2 www.ioannimamed.gr

  16. Chemotherapy (2) • Japanese phase III study: adjuvant chemo with S-1 (tegafur + oxonic acid) in stage II/III gastric cancer with LN dissection D2 • 3-year OS rate = 80.1% compared to 70.1% for surgery only • No data available with Western patients www.ioannimamed.gr

  17. Chemo for advanced/metastatic disease (1) • Provides palliation and improved survival • Single agents: 5-FU, mitomycin, etoposide, cisplatin – response rate = 10-20% • Other agents: irinotecan, paclitaxel, docetaxel, oral etoposide, oxaliplatin, UFT • Phase III study: irinotecan-containing regimen can be alternative when platinum-based therapy cannot be delivered (patients with advanced adenocarcinoma) www.ioannimamed.gr

  18. Chemo for advanced/metastatic disease (2) • Several randomized studies: • ECF offers improved median survival and quality of life compared to FAMTX and MCF regimens • FLO vs. FLP: FLO offers reduced toxicity, superior response rates, improved PFS & OS, improved time to treatment failure (age > 65 yrs) • Phase III study: DCF vs. CF • DCF offers longer time to progression • FDA approved (2006) DCF regimen for advanced gastric cancer treatment in patients with no prior chemo for advanced disease www.ioannimamed.gr

  19. Chemo for advanced/metastatic disease (3) • Phase III study: XP vs. FP as first-line treatment in untreated advanced gastric cancer • Capecitabine as effective as 5-FU in advanced GE cancers • Capecitabine-based combinations offer superior OS and similar PFS compared to 5-FU-based combinations www.ioannimamed.gr

  20. Targeted therapies • Poor prognosis associated with overexpression of EGFR/VEGFR/HER2 • Cetuximab/Bevacizumab/Trastuzumab have been evaluated in combination with chemo in advanced gastric adenocarcinomas • Phase III study: Trastuzumab in combination with cisplatin & fluoropyrimidine • Trastuzumab + chemo is the new standard of care for the treatment of HER2-expressing advanced gastric & GE cancers (improved median OS) www.ioannimamed.gr

  21. Workup (1) • Newly diagnosed patients : • H&P, • chest imaging, • upper GI tract endoscopy, • CBC, • chemistry profile, • abdominal CT with contrast, • pelvic CT scan or US (for women), • EUS (for potentially resectable cancer), • H.pylori testing and appropriate treatment www.ioannimamed.gr

  22. Workup (2) • Optional PET-CT scan: • Predicting response to preoperative chemo • Evaluation of recurrent gastric cancer • Demonstrating occult metastatic disease • Patient classification: • Localized cancer (Tis or T1a) • Locoregional cancer (stages I-III or M0) • Metastatic cancer (stage IV or M1) www.ioannimamed.gr

  23. Workup (3) – PRIMARY TREATMENT • Localized cancers (Tis/T1a): EMR or surgery • Potentially resectablelocoregional cancer (T1b): surgery www.ioannimamed.gr

  24. www.ioannimamed.gr

  25. Workup (4) – PRIMARY TREATMENT II • T2 or higher tumors: perioperative chemo with ECF regimen • Medically fit patients with unresectablelocoregional cancer/medically unfit patients with locoregional cancer: RT with concurrent fluoropyrimidine-based radiosensitization • Palliative chemo as an alternative option • For metastatic or locally advanced cancer • Regimens: • Primary => DCF, ECF(-modifications), Trastuzumab • Secondary => irinotecan + cisplatin, irinotecan + fluoropyrimidine, oxalipaltin +fluoropyrimidine, DCF modifications, paclitaxel-based regimen www.ioannimamed.gr

  26. www.ioannimamed.gr

  27. Workup (5) – PRIMARY TREATMENT III • Medically unfit patients/medically fit patients with unresectable disease: restaging and observation or surgery or palliative treatment www.ioannimamed.gr

  28. Workup (6) – POSTOPERATIVE TREATMENT • Based on surgical margins and nodal status • Patients with T3/T4/any node (+) tumors + R0 resection => RT & concurrent fluoropyrimidine-based radiosensitization + 5-FU (with or w/o leucovorin) or capecitabine • Same treatment for R1 resection patients • Patients with absence of M1 and R2 resection => RT & concurrent fluoropyrimidine-based radiosensitization or palliative chemo • Poor performance status patients => best supportive care www.ioannimamed.gr

  29. www.ioannimamed.gr

  30. Follow-up surveillance • Complete H&P: • Every 3-6 months for 1-3 yrs • Every 6 months for 3-5 yrs • Annually thereafter • CBC, chemistry profile, imaging studies or endoscopy if clinically indicated • After surgical resection: monitoring and indicated treatment for vitamin B12 and iron deficiency www.ioannimamed.gr

  31. Palliative chemo (1) • Considered for stage IV disease • Generally used: platinum agent + fluoropyrimidine regimens • Significant benefit from adding an anthracycline to the doublet => ECF among the most active and well-tolerated • Docetaxel increases the activity of 5-FU/cisplatin – more toxic in 3-weekly regimen • Irinotecan combined with 5-FU/LV can be considered in selected patients www.ioannimamed.gr

  32. Palliative chemo (2) • Substitution of capecitabine for 5-FU & oxaliplatin for cisplatin (ECF -> ECX/EOF/EOX): EOX offers longer OS than ECF and reduced thromboembolism rate • Meta-analysis: capecitabine superior to infused 5-FU for OS within doublet and triplet regimes for advanced gastric cancer www.ioannimamed.gr

  33. Palliative treatment for recurrent/metastatic disease (1) • Chemo + best supportive care vs. best supportive care for advanced gastric cancer: • OS: 8 vs. 5 months • Time to progression: 5 vs. 2 months • More patients with improved or prolonged high quality of life with chemo • Irinotecan vs. best supportive care in the second-line setting: prolonged OS • Offering or not chemo with best supportive care depends on patient’s PS www.ioannimamed.gr

  34. Palliative treatment for recurrent/metastatic disease (2) • For metastatic/locally advanced gastric cancer: • DCF(-modifications) • ECF(-modifications) • Irinotecan + cisplatin • Oxaliplatin + 5-FU or capecitabine • Irinotecan + 5-FU or capecitabine • Paclitaxel-based regimen • Trastuzumab www.ioannimamed.gr

  35. Best supportive care (1) • Palliative interventions for the management of bleeding, obstruction, pain, nausea, vomiting • Bleeding: • patients with hematemesis/melena => endoscopic assessment • When endoscopy not helpful => angiographic embolization • EBRT and/or endoscopy in patients with bleeding www.ioannimamed.gr

  36. Best supportive care (2) • Obstruction: • Gastrojejunostomy is most commonly used (preferable for patients with more prolonged prognosis) • Endoscopic placement of SEMS (relatively short life expectancy) • EBRT • Balloon dillation • Percutaneous endoscopic gastrotomy • Pain: • EBRT • Pain medication • Endoscopic removal of stent www.ioannimamed.gr

  37. J ClinOncol. 2004 Jun 1;22(11):2069-77. Epub 2004 Apr 13. • Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. • Department of Surgery, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands. h.h.hartgrink@lumc.nl • PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. • PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. • RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. • CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided. www.ioannimamed.gr

  38. Radiation and Chemotherapy After Surgery Improves Survival in Stomach Cancer • Postoperative chemotherapy and radiation treatment extended survival by an average of nine months in patients with operable cancer of the stomach or esophageal junction, according to research from a multicenter clinical trial published in the September 6, 2001, issue of the New England Journal of Medicine. An initial report of this trial was presented at the May 2000 meeting of the American Society of Clinical Oncology (ASCO). • The trial, conducted by the Southwest Oncology Group, involved 556 patients with cancer of the stomach or esophageal junction that could be removed by surgery. About 85 percent of patients in each group had cancer that spread to the lymph nodes in the gut, the first place stomach cancer tends to spread. • Study participants were randomly assigned to receive either surgery alone or surgery followed by chemotherapy with the drugs fluorouracil and leucovorin plus five weeks of radiation treatment. • After an average of five years of follow-up, average overall survival was 36 months in patients who received the adjuvant (additional) therapy, compared with 27 months in patients treated with surgery alone. Survival without return of stomach cancer was 30 months on average in the group receiving adjuvant therapy compared with 19 months in the surgery-only group. • Forty to 65 percent of patients suffer recurrences of cancer in the gastrointestinal region following surgery for stomach cancer. This high relapse rate makes it important to consider adjuvant therapy. However, in previous studies, adjuvant postoperative chemotherapy did not improve survival. Several small studies did suggest that postoperative radiation might extend survival. • In the current trial, the duration of survival in the surgery-only group was similar to that seen in other studies. "The apparent benefit of adjuvant therapy could not be the result of shorter-than-expected survival in the surgery-only group," principal investigator John S. Macdonald, M.D., and his colleagues reported. • Although adjuvant therapy extended patients' average overall survival by nine months, long-term survival was still low. Of the 281 patients who received adjuvant therapy, 169 died during the trial follow-up period, compared with 197 of the 275 patients who received surgery alone. Over half of the patients in the combination treatment group suffered toxic effects from the chemotherapy and radiation, and three patients died from those toxicities. • Among patients whose stomach cancer is detected at a very early stage, about 65 percent survive for 10 years, according to data from the National Cancer Data Base. Among patients with more advanced disease, 10-year survival ranges from 3 to 42 percent, depending on the extent of disease. Approximately 21,700 new cases of stomach cancer will be diagnosed among Americans in 2001, with men being at a slightly higher risk than women. • "Adjuvant treatment with fluorouracil plus leucovorin and radiation should be considered for all patients with high-risk gastric cancer," the researchers conclude. Current clinical trials continue to evaluate further ways of improving treatment for gastric cancer, including studying newer drugs and giving treatments prior to surgery. www.ioannimamed.gr

  39. N Engl J Med. 2006 Jul 6;355(1):11-20. • Perioperative chemotherapy versus surgery alone for resectablegastroesophageal cancer. • Department of Medicine, Royal Marsden Hospital, Sutton , Surrey, United Kingdom. • BACKGROUND: A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. • METHODS: We randomly assigned patients with resectableadenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. • RESULTS: ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). • CONCLUSIONS:In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival www.ioannimamed.gr

  40. Journal of Clinical Oncology, Vol 9, 827-831 • Sequential high-dose methotrexate and fluorouracil combined with doxorubicin--a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group • Laurentius Hospital, Roermond, The Netherlands. • In a prospective phase III multicenter trial, 213 patients with advanced measurable or nonmeasurable gastric cancer were randomized to receive methotrexate (MTX), fluorouracil (5-FU), and Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) (FAMTX) or 5-FU, Adriamycin, and mitomycin (FAM). The results show a significantly superior response rate (41% v 9% [P less than .0001]), and survival (median, 42 weeks v 29 weeks [P = .004]) for FAMTX. There was a cumulative thrombocytopenia in FAM and not in FAMTX. The FAMTX protocol should be the reference treatment in future clinical trials that seek to improve the therapeutic outcome in advanced gastric cancer. www.ioannimamed.gr

  41. J ClinOncol. 2006 Nov 1;24(31):4991-7. • Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. • University Hospital Gasthuisberg, Leuven, Belgium. • PURPOSE: In the randomized, multinational phase II/III trial (V325) of untreated advanced gastric cancer patients, the phase II part selected docetaxel, cisplatin, and fluorouracil (DCF) over docetaxel and cisplatin for comparison against cisplatin and fluorouracil (CF; reference regimen) in the phase III part. • PATIENTS AND METHODS: Advanced gastric cancer patients were randomly assigned to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 (day 1) plus fluorouracil 750 mg/m2/d (days 1 to 5) every 3 weeks or cisplatin 100 mg/m2 (day 1) plus fluorouracil 1,000 mg/m2/d (days 1 to 5) every 4 weeks. The primary end point was time-to-progression (TTP). • RESULTS: In 445 randomly assigned and treated patients (DCF = 221; CF = 224), TTP was longer with DCF versus CF (32% risk reduction; log-rank P < .001). Overall survival was longer with DCF versus CF (23% risk reduction; log-rank P = .02). Two-year survival rate was 18% with DCF and 9% with CF. Overall response rate was higher with DCF (chi2 P = .01). Grade 3 to 4 treatment-related adverse events occurred in 69% (DCF) v 59% (CF) of patients. Frequent grade 3 to 4 toxicities for DCF v CF were: neutropenia (82% v 57%), stomatitis (21% v 27%), diarrhea (19% v 8%), lethargy (19% v 14%). Complicated neutropenia was more frequent with DCF than CF (29% v 12%). • CONCLUSION: Adding docetaxel to CF significantly improved TTP, survival, and response rate in gastric cancer patients, but resulted in some increase in toxicity. Incorporation of docetaxel, as in DCF or with other active drug(s), is a new therapy option for patients with untreated advanced gastric cancer. www.ioannimamed.gr

  42. Ann Oncol. 2009 Sep;20(9):1529-34. Epub 2009 May 27. • Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. • The Royal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK. • BACKGROUND: The REAL-2 and ML17032 trials demonstrated that the oral fluoropyrimidine, capecitabine, is noninferior to 5-fluorouracil (5-FU) for overall survival (OS) and progression-free survival (PFS), respectively, in advanced oesophago-gastric cancer. • METHODS: Individual patient data were collected on all patients randomised within the trials (n = 1318). Kaplan-Meier survival curves were generated and the log-rank test was used to compare OS and PFS between patients receiving 5-FU combinations and capecitabine combinations. Stepwise multivariate Cox regression analysis was used to calculate corrected hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and PFS. Logistic regression was used for objective response rate. Forest plots with tests of heterogeneity were generated. • RESULTS: OS was superior in the 654 patients treated with capecitabine combinations compared with the 664 patients treated with 5-FU combinations; HR 0.87 (95% CI 0.77-0.98, P = 0.02). Poor performance status, age <60 and metastatic disease were independent predictors of poor survival. There was no significant difference in PFS between treatment groups on multivariate analysis. Assessable patients treated with capecitabine combinations were significantly more likely to have an objective response to treatment than those treated with 5-FU combinations; odds ratio 1.38 (95% CI 1.10-1.73, P = 0.006). • CONCLUSION: OS is superior in patients treated with capecitabine combinations compared with 5-FU combinations in advanced oesophago-gastric cancer. www.ioannimamed.gr

  43. Cancer Res Treat. 2010 Mar;42(1):24-9. Epub 2010 Mar 31. • Oxaliplatin, 5-fluorouracil and Leucovorin (FOLFOX-4) Combination Chemotherapy as a Salvage Treatment in Advanced Gastric Cancer. • Division of Hematology/Oncology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea. • PURPOSE: This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC). • MATERIALS AND METHODS: The AGC patients with an ECOG performance status of 0~1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m(2) on day 1), leucovorin (200 mg/m(2) on days 1 and 2) and 5-fluorouracil (400 mg/m(2) as a bolus and 600 mg/m(2) as a 22-hour infusion on days 1 and 2) every 2 weeks. • RESULTS: For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1~12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progression-free survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable. • CONCLUSION: Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status. www.ioannimamed.gr

  44. Journal of Clinical Oncology, Vol 17, Issue 12 (December), 1999: 3810-3815 • Randomized Clinical Trial of Adjuvant Mitomycin Plus Tegafur in Patients With Resected Stage III Gastric Cancer • Medical Oncology Unit, Hospital Mútua de Terrassa-Universitat de Barcelona, Plaça Dr Robert 5, 08221 Terrassa, Barcelona, Spain • PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. • PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. • RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. • CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer. www.ioannimamed.gr

  45. Journal of Clinical Oncology, Vol 12, 2687-2693 • Fluorouracil, doxorubicin, and mitomycin combination versus PELF chemotherapy in advanced gastric cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research • Medical Oncology Institution of Parma, Italy. • PURPOSE: The combination of cisplatin, epirubicin, and leucovorin preceding fluorouracil (PELF) includes three novel agents compared with the standard combination of fluorouracil, doxorubicin, and mitomycin (FAM) in the treatment of advanced gastric carcinoma. We report the results of a prospective randomized comparison of the two combinations in previously untreated patients. • PATIENTS AND METHODS: One hundred thirty assessable patients were entered onto the trial; 52 received FAM and 85 PELF. A 1:2 unbalanced randomization in favor of the experimental treatment was chosen. Approximately 90% of patients had measurable tumor masses. • RESULTS: The overall response rates (complete responses [CRs] and partial responses [PRs]) were 15% and 43% for the FAM and the PELF regimens, respectively, with a statistically significant advantage for the experimental treatment (P = .001). Time to progression (median, 2.6 and 4.7 months), duration of response (median, 10.7 and 10.2 months), and survival durations (median, 5.6 and 8.1 months) were not significantly different between the FAM and PELF regimens, respectively. The PELF combination was more toxic compared with FAM, but generally tolerable. • CONCLUSION: This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses. Due to tolerability, it is not recommended for routine clinical use. However, it should be considered, among other second-generation chemotherapy combinations, in future randomized studies aimed to improve the therapeutic outcome in gastric carcinoma. www.ioannimamed.gr

  46. Thank you www.ioannimamed.gr