High curative resection rate with weekly cisplatin, 5-fluorouracil, epidoxorubicin, 6S-leucovorin, glutathione, and filgastrim in patients with locally advanced, unresectable gastric cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS 相似文献   

Adjuvant chemotherapy for unresectable locally advanced pancreatic cancer in light of its characteristics

The use of neoadjuvant chemotherapy for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors, especially for patients with Stage IV b (Japan criteria). We report our experience with a six-drug chemotherapeutic regimen that resulted in sufficient downstaging of the tumor in some patients to justify surgical resection. From Jan. 2001 through December 2003, 6 patients received 5-FU as a continuous infusion (200 mg/m2/day), calcium leucovorin weekly by intravenous bolus injection (30 mg/m2), mitomycin-C every 6 weeks (10 mg/m2 intravenously), and dipyridamole daily orally (75 mg), according to the UCLA regimen and gemcitabine weekly (600 mg/m2) and heparin as a continuous infusion (0-3,000 U/day) for locally advanced unresected pancreatic cancer. All of these patients were evaluable for response and survival. There were 5 partial responses (83% response rate) and 1 no response. Four of 5 responding patients had sufficient tumor regression to meet clinical criteria for resectability, three of whom underwent a curative resection. All patients who underwent downstage operation were still alive for the follow-up period (4-23 months).     

Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) as neoadjuvant chemotherapy in gastro-oesophageal cancer.

High response rates have been reported in the treatment of advanced gastric cancer with epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF), including instances of unresectable disease being rendered operable by chemotherapy. We report our experience with ECF as neoadjuvant treatment in gastric and lower oesophageal carcinoma. Twenty-seven patients were treated, of whom ten (37%) had carcinoma of the stomach and 17 (63%) tumours of the lower oesophagus. Histology in the majority of cases, 21 (78%), was adenocarcinoma. Before chemotherapy ten patients (37%) had evidence of initially unresectable locally advanced disease, 16 (59%) had localised disease only and one patient (4%) had a localised primary with a single liver metastasis. Epirubicin (50 mg m(-2) i.v.) and cisplatin (60 mg m(-2) i.v.) were administered every 3 weeks for four cycles together with a continuous 12 week infusion of 5-fluorouracil (200 mg m(-2) day(-1)). Fifteen of 24 assessable patients (62%) had symptomatic improvement on chemotherapy. On combined surgical and/or radiological assessment, 15 of the 27 patients (56%) had objective evidence of tumour response. In all patients assessment for radical surgery was made following chemotherapy. Eighteen patients (67%) proceeded to operation: of these, 11 had complete resection of their disease, one had a histologically incomplete resection and six were found to have unresectable disease. No pathological complete responses were observed. Only one of the ten patients with locally advanced disease achieved complete surgical resection after chemotherapy. At a median follow-up of 36 months from date of diagnosis (range 30-47 months), 19 of the 27 patients (70%) have died. Of 11 patients who had a complete surgical resection, one died post-operatively, three have subsequently relapsed (of whom two have died) and seven remain disease free. Toxicity from treatment was mild and included emesis, myelosuppression, stomatitis and exfoliation. Myelosuppression caused modification of treatment in 14 of 108 chemotherapy cycles (13%). There was one surgical death but no chemotherapy-related deaths. These early results show encouraging symptomatic and objective responses of gastro-oesophageal carcinoma to ECF, but provide no instances of ECF achieving complete pathological response. Only randomised trials can establish the role of neoadjuvant ECF chemotherapy in both initially resectable and unresectable carcinoma of the stomach and lower oesophagus.     

Phase II trial of preoperative S-1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer

Background

The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer.

Methods

We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m² divided in two daily doses for 21 days and cisplatin at 60 mg/m² intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy.

Results

Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes.

Conclusions

Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.     

Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer.

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.     

不能切除和复发的局部进展期胃癌放疗疗效分析

目的 回顾分析不能切除和复发的局部进展期胃癌行腹部放疗的疗效及影响因素。方法 回顾分析2009—2015年我院收治的57例患者,其中不能切除36例(包括局部晚期19例、术后肉眼残留17例),术后复发21例。接受3DCRT 17例、IMRT 40例,照射中位剂量50 Gy (42~60 Gy)。81%患者放疗同期口服氟尿嘧啶类药物化疗。结果 全组患者放疗后中位随访时间为16个月(3.9~77.5个月),放疗后缓解率65%。局部晚期、术后肉眼残留(R₂术后) 、术后复发组放疗后中位生存时间分别为13.9、13.9、19.0个月。全组放疗后2年的预期OS、PFS、LRRFS分别为50%、37%、50%。多因素分析显示病变分组是预后影响因素,而第3站淋巴结受侵并不是不良预后因素。结论 对不能切除及术后复发的局部进展期胃癌进行中等剂量放疗并结合化疗能取得较好的LC并改善患者生存,而术后复发和第3站淋巴结受侵病例均应被视为挽救性放化疗的良好适应征。     

A partial response to combined TS-1 and docetaxel chemotherapy enabling a curative resection after the failure of combined TS-1 and CDDP chemotherapy in a patient with unresectable gastric cancer

A 60-year-old man visited our hospital complaining of epigastric pain. Gastrofiberscopy revealed an advanced gastric cancer located on the anterior wall of the antrum. Abdominal computed tomography (CT) revealed metastases to the paraaortic lymph nodes. The patient subsequently underwent combined chemotherapy consisting of TS-1 and low-dose CDDP for the treatment of unresectable gastric cancer. No reductions in the paraaortic lymph node metastases were noted after one cycle. The patient was then treated with TS-1 combined with docetaxel as a second-line chemotherapy. TS-1 (80 mg/m2) was orally administered for 2 weeks followed by a 2 week interval, while docetaxel (25 mg/m2) was simultaneously administered weekly (days 1, 8, and 15). One cycle of chemotherapy was 28 days. An abdominal CT revealed a partial response after 3 cycles. The patient experienced grade 2 leukocytopenia and grade 3 neutropenia. We decided that the patient could undergo a curative resection, and a distal gastrectomy with D2+para-aortic LN dissection was performed. The pathological efficacy was Grade 2. The patient is presently alive with no sign of recurrence after 20 months. Combined TS-1 and docetaxel chemotherapy is a promising second-line regimen for the treatment of unresectable gastric cancer, after treatment with TS 1 combined with CDDP has failed.     

Efficacy and Tolerability of Weekly Docetaxel,Cisplatin, and 5-Fluorouracil for Locally Advanced or Metastatic Gastric Cancer Patients with ECOG Performance Scores of 1 and 2

Background: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliativeregimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluatethe efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancerpatients. Materials and Methods: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG(Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least twocycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocolincluded 25mg/m2 docetaxel, 25mg/m2 cisplatin, and 24 hours infusion of 750mg/m2 5-fluorouracil, repeated everyweek. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related totreatment, progression free survival (PFS) and overall survival (OS) were evaluated. Results: Of the patients, 41were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observedin 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was notedin 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survivalwas 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9%had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renaltoxicity (7.8%) and thrombosis (1.6%). Conclusions: In patients with locally advanced or metastatic gastriccancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstratedmodest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment optionfor such patients.     

Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients (excluding patients who were T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated. PATIENTS AND METHODS: From January 1993 to December 1994, 252 patients were enrolled into the study and allocated randomly to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2. The primary end point was relapse-free survival. Overall survival and the site of recurrence were secondary end points. RESULTS: Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection. There were no treatment-related deaths and few serious adverse events. There was no significant difference in relapse-free and overall survival between the arms (5-year relapse-free survival 88.8% chemotherapy v 83.7% surgery alone; P =.14 and 5-year survival 91.2% chemotherapy v 86.1% surgery alone; P =.13, respectively). Nine patients (7.1%) in the chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer recurrence. CONCLUSION: There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection, and there was no statistical difference between the two arms relating to the types of cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice.     

Chemoradiotherapy in the treatment of regional pancreatic carcinoma: a phase II study

In locally advanced pancreatic cancer, the utilization of chemotherapy and radiotherapy is increasing, although in view of the reported long-term results of several contemporary trials, further improvements are certainly needed. Encouraging results using the combination of cisplatin, cytarabine, caffeine, and continuous infusion (CI) 5-fluorouracil (5-FU) (PACE) for the treatment of advanced pancreatic carcinoma prompted a phase II study using PACE followed by external beam radiotherapy with CI of 5-FU (PACE-RT) for localized disease. Forty-one patients were treated with PACE-RT as adjuvant therapy after surgical resection (21 patients), or as primary therapy for locally advanced, unresectable disease (20 patients), with reevaluation for resection after completion of treatment. PACE consisted of cisplatin 100 mg/m2 IV on day 1, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and days 3 to 21, 5-FU 250 mg/m2/d given by CI. Cycles were repeated every 28 days. After 2 cycles of PACE, radiation therapy was given concurrently with 5-FU at 200 mg/m2/d. In the adjuvant setting, the tumor bed and the draining lymph node basin received 50.4 Gy and 45 Gy, respectively. In the neoadjuvant setting, the primary and regional lymph nodes were to receive 39.6 Gy followed by a neutron boost of 8 NGy to the gross tumor volume. Photon therapy was delivered at 1.8 Gy per fraction and neutron therapy at 0.8 NGy per fraction, 5 days a week. All patients were evaluable for toxicity and survival. The most common toxicity was myelosuppression, with grade III to IV neutropenia occurring in 59% of the patients. The median survival times in the locally advanced and adjuvant patients were 13.4 and 18.1 months, with 1-year survival rates of 52% and 65%, respectively. Nine of 20 patients receiving PACE-RT for unresectable carcinoma had sufficient tumor regression to meet clinical criteria for exploration; three were resected with curative intent. The survival of these three patients undergoing resection after neo-adjuvant therapy was 22.4, 24.3 and 40 months. The treatment program was active, but only moderately well tolerated. Modification of this regimen with newer, less toxic drugs may provide better results and reduced toxicity.     

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.     

Results of radiation therapy in gastric cancer

Radiation therapy has been used in the treatment of patients with gastric cancer in two clinical settings: definitive therapy for locally advanced, unresectable tumors and adjuvant therapy following surgery for high-risk disease. For patients with locally advanced, unresectable or subtotally resected gastric carcinoma, radiotherapeutic approaches with and without chemotherapy have been employed, because these tumors appear localized, without clinically detectable metastases. Combined treatment with radiation therapy and chemotherapy appears to prolong survival but rarely results in long-term cure. Although only a modest effect was seen on survival, importantly, these studies established the foundation of contemporary combined-modality therapy and have served to stimulate further clinical investigation in gastric cancer as well as other gastrointestinal disease sites. For patients undergoing resection and lymphadenectomy with curative intent, the development of local or regional failure is common, occurring in 40% to 65% of patients. Sites of local and regional failure following resection include the gastric/tumor bed in 20% to 55%, the anastomosis in 25% to 50%, and the regional nodes in 40% to 50% of patients. Intergroup Trial 0116 (INT 0116), a phase III trial, has recently demonstrated that adjuvant radiation therapy with concurrent and maintenance 5-fluorouracil (5-FU) and leucovorin (LV) reduces local failure and improves survival. Adjuvant therapy is now routinely administered to patients undergoing resection of gastric cancer for high-risk disease. Ongoing trials are now investigating new systemic agents with radiation therapy to establish efficacy compared to 5-FU and LV, as well as evaluating neoadjuvant approaches prior to resection.     

Phase III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and polyadenylic-polyuridylic acid (poly A:U) for locally advanced gastric cancer after curative surgery: final results of 15-year follow-up.

BACKGROUND: This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and polyadenylic-polyuridylic acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. PATIENTS AND METHODS: From 1984 to 1989, patients who had D(2-3) curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. RESULTS: A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2-T4a), and lymph node status (N0-N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. CONCLUSIONS: These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.     

A case of liver metastasis from gastric cancer responding to S-1/CDDP chemotherapy, allowing partial gastrectomy and left hepatectomy

A 63-year-old man was found to have an upper abdominal mass, and was referred to our hospital. Endoscopic examination and abdominal CT showed gastric cancer with liver metastasis. A large metastatic tumor of the liver invaded the hepatic hilus, making curative resection impossible. We started chemotherapy using S-1(120 mg/body/day), orally administered for three weeks followed by 2-week rest period, and cisplatin(100mg/body), administered intravenously on day 8 as 1 course. After 5 courses of chemotherapy, the liver tumor reduced markedly and the gastric cancer pathologically disappeared, enabling partial gastrectomy and left hepatectomy. Histological examination showed a well-differentiated adenocarcinoma in the mucosal layer of the resected stomach. A resected specimen of the liver showed a moderately-differentiated adenocarcinoma with signet-ring cells, compatible to liver metastasis from gastric cancer. Bile leakage the remaining liver occurred, but he recovered soon. Gastrointestinal examination revealed another early gastric cancer after seeing him for 2 years on an outpatient basis. We conducted subtotal gastrectomy, and the patient remains alive 30 months after the first operation. This case suggests that S-1/CDDP chemotherapy may reduce the stage of unresectable liver metastasis from gastric cancer and make a curative operation possible.     

Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.     

Helicobacter pylori infection as an independent prognostic factor for locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection

A few studies reported the association between negative Helicobacter pylori infection and poor clinical outcome in resected gastric cancer patients. We investigated the H. pylori infection status and its association with the clinical outcome in 274 locally advanced gastric cancer patients (American Joint Committee on Cancer stage IB: 25, II: 82, IIIA: 80, IIIB: 39 and IV: 48) who underwent adjuvant chemotherapy after curative resection (≥ D2 dissection). H. pylori infection status in hematoxylin and eosin stained corporal and antral mucosa of non-tumor tissue was graded according to the updated Sydney System and categorized as H. pylori negative (normal or mild infection) and H. pylori positive (moderate or marked infection). Eighty-one patients received 5-fluorouracil (5-FU) and doxorubicin-based chemotherapy, while 193 patients underwent 5-FU, mitomycin-C and polysaccharide-K chemotherapy. The median follow-up duration of survivors was 144 (120-184) months. In univariate analysis, patients with H. pylori negative status (108 patients) demonstrated significantly poor 10-year overall survival (OS) compared to those with H. pylori-positive status (166 patients; 21.3% vs. 71.1%, p < 0.0001). H. pylori negative status was associated with poor outcome in all stages except stage IIIB. In multivariate analysis, H. pylori-negative status was the most significant independent prognostic factor of poor OS (hazard ratio: 3.45, 95% confidence interval: 2.43-4.89, p < 0.0001) followed by old age (>54 years, p < 0.0001), advanced stage (stage III or IV, p = 0.001), and Borrmann type IV (p = 0.027). H. pylori infection status seems to have strong prognostic significance in locally advanced gastric cancer. H. pylori-negative patients may need careful follow-up after curative resection.     

Intensive weekly chemotherapy is not effective in advanced pancreatic cancer patients: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

Twenty-two patients, with locally advanced unresectable and/or metastatic pancreatic carcinoma, received weekly administration of cisplatin 40 mg m(-2), 5-fluorouracil 500 mg m(-2), epidoxorubicin 35 mg m(-2), 6S stereoisomer of leucovorin 250 mg m(-2) and glutathione 1.5 mg m(-2), supported by a daily administration of lenograstim at a dose of 5 microg kg(-1). Nineteen patients were men and three were women. Median age was 63 years (range 47-70). At study entry, pain was present in 15 out of 22 patients (68%) with a mean value of Scott-Huskisson scale of 27.6+/-23.8, whereas a weight loss >10% was present in 15 patients. After eight weekly treatments, three partial responses were achieved for a response rate of 13% (95% CI 0-26%), five patients had stable disease and 14 progressed on therapy. Pain was present in 9 out of 22 patients (40%) with a mean value of Scott-Huskisson scale of 12.3+/-18.4. Eight patients (36%) (three partial response and five stable disease) had a positive weight change. Toxicity was mild: WHO grade III or IV toxicity was recorded in terms of anaemia in 7 out of 188 cycles (3.7%), of neutropenia in 9 out of 188 cycles (4.7%) and of thrombocytopenia in 3 out of 188 cycles (1.5%). Median survival of all patients was 6 months. The outcome of this intensive chemotherapy regimen does not support its use in pancreatic cancer.     

Phase II trial of primary radiation therapy and concurrent chemotherapy for patients with locally advanced pancreatic cancer

OBJECTIVES: Primary chemoradiotherapy for locally advanced pancreatic cancer (LAPC) may improve local control, curative resection rate and long-term survival. We performed a phase II study to evaluate toxicity and activity of primary radiation therapy and concurrent chemotherapy with gemcitabine (GEM) twice weekly in patients (pts) with LAPC. METHODS: From 6/1999 to 6/2003, 23 LAPC pts received GEM 100 mg/m2 twice weekly in the first 15 pts and 50 mg/m2 in the last 8 pts, concurrently with radiotherapy (1.8 Gy/day for a total dose of 45 Gy). RESULTS: The treatment was completed in 19/23 pts. Toxicities: G3-4 hematological toxicity occurred in 35 and 4% respectively; G3 nausea and vomiting and gastrointestinal toxicity in 30%. Clinical benefit was found in 10/18 pts (55%). Overall response: partial response rate 4/18 (22%); stable disease 13/18 (72%); progressive disease 1/18 (6%). Six pts underwent pancreaticoduodenectomy with extended lymphadenectomy (5/6 pts pT3, 1/6 pts microscopic cancer foci, 1/6 N+, 5/6 negative retroperitoneal margin). MEDIAN SURVIVAL: 14 months for the entire group, 12 months for unresected pts, 20 months for resected pts. CONCLUSIONS: The treatment with GEM twice weekly at 50 mg/m2 associated with radiotherapy (45 Gy) is feasible and permits to obtain clinical benefit in a good percentage of pts. Objective response, median survival, and local and systemic control are similar to other studies and need further improvement.     

A case of stage IV gastric cancer treated sequentially for over two years by TS-1, paclitaxel, and CPT-11

We report a patient with advanced stage IV gastric cancer treated by chemotherapy for over two years. The patient was a 69-year-old man with paraaortic lymph node metastasis of gastric cancer. He underwent a distal gastrectomy in non-curative resection. After surgery, chemotherapy with TS-1 (100 mg/body/day) was performed. At 7 months after surgery, progression of lymph node metastasis in porta hepatis was recognized, and paclitaxel was administered at a weekly dose of 80 mg/m(2) for 3 weeks followed by one week rest. He remained stable for 12 months under paclitaxel treatment. At 26 months after surgery, progression of lymph node metastasis in porta hepatis was recognized again, and CPT-11 was administered at a bi-weekly dose of 80 mg/m(2). Although the patient died two years seven months after surgery, the chemotherapy with sequential administration of TS-1, paclitaxel and CPT-11 was thought to be effective for advanced gastric cancer.     

Curative resection of advanced gastric cancer responding to preoperative chemotherapy--a case report

A 56-year-old male was admitted for treatment of advanced gastric cancer. The patient was diagnosed as having an unresectable advanced gastric cancer because cancer cells had invaded the pancreas head and there were metastatic lymph nodes. The patient underwent preoperative chemotherapy (FLEP: intra-arterial infusion of CDDP, ETP and intravenous infusion of 5-FU, LV). The primary tumor and metastatic lymph nodes were reduced by three course of chemotherapy. The patient underwent curative resection and survived without recurrence for 14 months after operation. Preoperative chemotherapy using FLEP was performed in 15 patients with unresectable primary advanced gastric cancer. This therapy resulted in significantly higher survival times. In conclusion, FLEP has been shown to be effective for unresectable advanced gastric cancer.