Phase II study of FOLFOX4 with "wait and go" strategy as first-line treatment for metastatic colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of FOLFOX4 using "wait and go" strategy in treating metastatic colorectal cancer. METHODS: The conventional FOLFOX4 was repeated every 2 weeks. We waited until the recovery of symptoms from persistent neurotoxicity within an added period of 2 weeks, before performing the next cycle ("wait and go" strategy). RESULTS: We enrolled 58 patients, in whom a total of 481 cycles were administered (median 8 per patient; range 1-16). Toxicity was evaluated in 58 patients and response in 55. The major toxic effect was grade 3/4 neutropenia (33%). Painful paresthesia or persistent functional impairment was observed in 4 patients (7%). The response rate was 40% (95% confidence interval; 27.1-52.9%). The median progression-free survival time was 10.2 months, the 1-year survival rate was 89%, and the median overall survival time was 27.6 months. CONCLUSIONS: These findings indicate that this "wait and go" strategy reduces the frequency of persistent neuropathy while maintaining efficacy against metastatic colorectal cancer.

Stroke volume variation as a predictor of intravascular volume depression and possible hypotension during the early postoperative period after esophagectomy.

BACKGROUND: Perioperative hypotension during esophagectomy results from hypovolemia caused by a shift of extracellular fluid from the intravascular to the extravascular compartment. Fluid management is often difficult to gauge during major surgery because there are no reliable indicators of fluid status, and some patients still experience cardiorespiratory instability. In this retrospective study, we evaluated stroke volume variation (SVV), calculated by using a new arterial pressure-based cardiac output measurement device, as a predictor for fluid responsiveness after esophageal surgery. METHODS: Eighteen patients undergoing esophagectomy with extended radical lymphadenectomy were monitored by the FloTrac sensor/Vigileo monitor system during the perioperative and immediate postoperative period. Fluid responsiveness was assessed and compared with concurrent SVV and central venous pressure (CVP) values, and routine hemodynamic variables. RESULTS: Eleven of 18 patients needed additional volume loading within the first 10 postoperative hours as a result of hypotension. The maximum SVV value of fluid resuscitated patients was >15% in all cases, whereas six of seven patients without postoperative hypotension had maximum SVV values of <15%. The correlation between SVV and the development of hypotension was statistically significant (P = 0.0012). From the linear correlation analysis of hemodynamic variables influenced by additional fluid loading, SVV was significantly correlated to cardiac output (r = 0.638; P = 0.049), whereas CVP was not (P > 0.05). CONCLUSION: We conclude that SVV, as displayed on the Vigileo monitor, is an accurate predictor of intravascular hypovolemia and is a useful indicator for assessing the appropriateness and timing of applying fluid for improving circulatory stability during the perioperative period after esophagectomy.

Perioperative monitoring of fluid responsiveness after esophageal surgery using stroke volume variation.

OBJECTIVE: To assess the utility of a new arterial pressure-based cardiac output (FloTrac) and central venous oximetry (PreSep) monitoring system in the perioperative management of patients undergoing radical esophagectomy. CASE SERIES: From May 2006, a new analyzing device (Vigileo monitor; Edwards Lifesciences LLC, Tokyo, Japan), which can be used in combination with the FloTrac and PreSep sensors, has been used in nine patients who have undergone radical operations for thoracic esophageal cancer at our hospital. Stroke volume variation (SVV), calculated for each respiratory cycle and displayed on the Vigileo monitor, precisely predicted intravascular hypovolemia. The maximum SVV of patients who needed fluid resuscitation was significantly higher than that of patients who had a stable circulation. The mean value of the maximum SVV in the patient with or without fluid resuscitation was 25 +/- 6.9 and 13 +/- 1.4%, respectively (p < 0.04). In addition, continuous monitoring of central venous oxygen saturation enabled evaluation of oxygen supply to tissues to aid in determining the need for red blood cell transfusion. The Vigileo monitor (with Flo Trac and PreSep sensors) provided reliable information for the perioperative management of high-risk patients after highly invasive general surgery without the need for an invasive central or pulmonary catheter.

[A case of advanced gastric cancer successfully treated with TS-1/CDDP combination chemotherapy, able to maintain CR for more than two years against multiple liver metastases].

INTRODUCTION: In recent years, a high success rate of combination chemotherapy with TS-1/CDDP has been reported against advanced gastric carcinoma. We, this time, experienced a case of advanced hemorrhagic gastric cancer with multiple hepatic metastases for which total gastrectomy was performed, followed by postoperative combination chemotherapy with TS-1/CDDP which culminated in achieving CR for the liver metastases. CASE REPORT: The patient was a 59-year-old woman who was hospitalized for a type IV gastric carcinoma in the upper part of the gastric body. Further examination revealed liver (S 2, S 5, S 7) and lymph node metastases. Due to hemorrhage from the tumorous lesion, the treatment strategy selected was total gastrectomy followed by postoperative chemotherapy. Operative and clinicopathological findings revealed a mass lesion of MLU, type IV, 16.0x14.0 cm, sT 3 (SE), sH 1 (bilobular multiple metastases) and CY 0, and por 1, pT 2 (SS), pN 1 (+) [23/38], int, INF beta, ly 3 and v 1, respectively. Combination chemotherapy with TS-1/CDDP was instituted after surgery. As for the dosing method of combination chemotherapy,the patient was treated with a course of TS-1 80 mg daily divided into two doses over 21 days continuously, followed by a 14-day cessation of the drug,together with a dose of CDDP 70 mg on day 8. The patient received a total of four courses. At the completion of the third chemotherapy course, her multiple hepatic metastases disappeared. Further, the preoperative CA 19-9 level of 370 U/mL returned to normal after chemotherapy. Adverse events observed were leukopenia and thrombocytopenia, both of which were judged to be grade 2. At two years and nine months, the patient is being followed on an outpatient basis without any sign of postoperative recurrent disease. CONCLUSION: We experienced a patient who was successfully treated with combination chemotherapy and demonstrated disappearance of her multiple hepatic metastases, showing a clinical response of CR lasting for more than two years against the metastases. It was inferred that this regimen of TS-1/CDDP is an effective treatment modality not only as preoperative but also postoperative chemotherapy after surgery for advanced gastric carcinoma.

[A case of advanced gastric cancer which became operable after chemotherapy with combination of TS-1/CDDP and in which complete disappearance of liver metastasis was histopathologically confirmed].

We encountered a patient in whom TS-1/cisplatin (CDDP) combination chemotherapy was effective. The cancer became operable, and complete disappearance of liver metastasis was histopathologically confirmed. The patient was a 65-year-old man who presented with complaints of epigastric discomfort and anorexia. Based on upper GI endoscopy and abdominal CT, type 1 gastric cancer associated with liver and abdominal lymph node metastases was diagnosed. The cancer was judged to be inoperable, and chemotherapy with a combination of TS-1 and CDDP was initiated. One course of treatment consisted of administration of 120 mg/day of TS-1 for 21 days followed by 14 days of withdrawal, and administration of 100 mg/body/day of CDDP on day 8 (80 mg/body/day in the second course). After two courses of treatment, the primary lesion and the liver and lymph node metastatic lesions decreased in size (reduction ratios were 42.3%, 90.5% and 85.2%, respectively). The tumor marker values became normal. Subsequently, the cancer was judged to have become operable. After consultation with the patient, total gastrectomy, splenectomy, partial hepatectomy, and D3 dissection were performed, and curability B was achieved. The only adverse event of Grade 2 or more severity observed during drug administration was anorexia. Liver metastasis was judged from pathological findings to have disappeared. The postoperative course was uneventful and the patient was discharged from the hospital. To date, there have been no signs of recurrence. TS-1/CDDP therapy is believed to provide effective treatment against liver metastasis and lymph node metastasis of gastric cancer.