Cycles Of FOLFOX Research Articles

Clinical randomized study of postoperative radiochemotherapy compared with chemotherapy alone in the treatment of locally advanced gastric cancer

Objective To investigate the efficacy and toxicity of postoperative radiochemotherapy compared with chemotherapy alone in the treatment of locally advanced gastric cancer.Methods A total of 83 patients with resected adenocarcinoma of the stomach were randomly assigned to postoperative radiochemotherapy group (RCT) ( n =43 ) or chemotherapy alone group (CT) ( n =40 ).Patients in RCT group received radiotherapy concurrent with capecitabine chemotherapy then followed by 4 - 6 cycles of FOLFOX4 chemotherapy.The total dose of radiation was 45 Gy.The dose of capecitabine was 1600 mg/m2per day.In the CT group,patients received 6 - 8 cycles FOLFOX4 chemotherapy.Survival was analyzed using Kaplan-Meier method and Logrank test. Results The follow-up rate was 96％. The number of patients who had a minimum of 2-,3-year follow-up time were 37,12 in the RCT group and 31,10 in the CT group.The 1-,2-,3-year local control rates for RCT and CT groups were 100％,97％,94％ and 95％,87％,73％ (x2 =4.54,P =0.033),respectively.The 1-,2-,3-year survival rates were 98％,86％,81％ in the RCT group,with 93％,80％,64％ in the CT group ( x2 =3.96,P =0.047 ).The incidence of grade 3hematological toxicity in the RCT and CT group was 23％ vs 15％ ( x2 =0.93,P =0.630 ),and grade 3gastrointestinal toxicity was 16％ vs 10％ ( x2 =0.95,P =0.624 ). Conclusions Compared with chemotherapy alone,postoperative radiochemotherapy can improve survival of locally advanced gastric cancer patients with acceptable toxicities. Key words: Gastric neoplasms/radiotherapy; Gastric neoplasms/chemotherapy; Combined modality therapy; Prognosis

Irinotecan Drug-Eluting Beads in the Treatment of Chemo-Naive Unresectable Colorectal Liver Metastasis with Concomitant Systemic Fluorouracil and Oxaliplatin: Results of Pharmacokinetics and Phase I Trial

PurposeThe primary objective of this study is to evaluate the safety, tolerance, and pharmacokinetic profile of liver-directed therapy with drug-eluting beads irinotecan (DEBIRI) in combination with systemic modified FOLFOX in the treatment of unresectable liver metastases in chemotherapy-naive patients with colorectal cancer. DesignDEBIRI, loaded with 100 mg irinotecan (100–300μm beads), was administered via hepatic artery during the off week of FOLFOX therapy. Primary endpoints were safety, tolerance, systemic dose-limiting toxicities, and pharmacokinetics of systemic irinotecan and its active metabolite SN-38 at each infusion at 1-, 4-, and 24-h post-DEBIRI. Secondary endpoints were response rate and survival. ResultsThe ten patients have undergone at least 12 cycles of FOLFOX in combination with at least two DEBIRI bead treatments during the patients’ off week. Pharmacokinetic data has demonstrated minimal detectable levels of irinotecan (18.6, 21, and 18.6 ng/ml) and SN-38 (1.06, 1.47, and 1.55 ng/ml) after the first, second, and third DEBIRI treatments, respectively. Currently, there has been only one severe device-related adverse event, a grade 3 hypertensive episode that required 1 day of observation in the hospital. The initial 9- and 12-month response rates have been 100 % (2 CR, 8 PR). Four (40 %) patients were successfully downstaged to resection and/or ablation with a median overall survival of 15.2 months. ConclusionConcomitant DEBIRI and FOLFOX±bevacizumab is safe, with a minimal adverse event rate, no dose-limiting toxicities, and enhanced overall response rate.

Postoperative Adjuvant Radiochemotherapy for Patients with Stage III or IV Gastric Cancer

Background and Purpose: It is known that radiotherapy or chemotherapy alone don't represent a standard of care as adjuvant treatment for patients with advanced gastric cancer that underwent surgical resection. The purpose in the approach of this cancer is to find an adjuvant treatment that can affect overall survival. Phase 2 studies and randomized trials suggest that a multimodal approach with chemo radiotherapy (CT-RT) can improve overall survival. We analyze the feasibility and toxic effects of chemo radiotherapy (CT-RT) as a post surgical adjuvant treatment in a cohort of patients with high risk gastric cancer. Methods: We enrolled 48 patients with advanced gastric cancer (Stage III and IV, M0). These patients were submitted to surgical resection and all of them, within 6 weeks, underwent adjuvant chemotherapy with FOLFOX-4 (ie, a combination of folinic acid, fluorouracil, and oxaliplatin) for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy started after the first 2 cycles of FOLFOX-4. Chemotherapy schedule was reduced by 25% during the period of the contemporary radiotherapy treatment. Results: All patients except one ended the combined adjuvant treatment. We observed severe hematologic adverse effects only in less than 10% of patients (4 patients); regarding gastrointestinal toxic effects they occurred in 33% of patients and specifically we noted G1-G3 grade toxicity and no G4 toxicity . Disease-free and overall survival at 1, 2, and 3 years was superior to in untreated patients. One to 3-years Median disease-free and overall survival rates were 27 months and 15 months respectively. Conclusions: A combined trial with chemo radiotherapy (CT-RT ) as adjuvant treatment represents an effective approach for patients with resected advanced gastric cancer.

Oxaliplatin induced disseminated intravascular coagulation: A case report and review of literature

Oxaliplatin in combination with a fluoropyrimide is a treatment option for colorectal cancer patients in the adjuvant and metastatic settings. Very few hematological emergencies have been reported associated with Oxaliplatin. These include autoimmune hemolytic anemia, thrombocytopenia and pancytopenia. We present a case report of a patient who developed hematuria and disseminated intravascular coagulation while receiving the second cycle of FOLFOX and bevacizumab for metastatic colon cancer.

Bevacizumab-Induced Reversible Thrombocytopenia in a Patient with Adenocarcinoma of Colon: Rare Adverse Effect of Bevacizumab

We report a case of bevacizumab- (BEV-) induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin) regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) regimen along with BEV 10 mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets.

Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial.

To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed.

High-intensity focused ultrasound as a treatment for colorectal liver metastasis in difficult position

High-intensity focused ultrasound as a treatment for colorectal liver metastasis in difficult position

Yiqi Zhuyu Decoction (益气逐瘀汤) Combined with FOLFOX-4 as first-line therapy in metastatic colorectal cancer

To evaluate the efficacy and safety of yiqi zhuyu decoction (YZD) combined with oxaliplatin plus 5-flurouracil/leucovorin (FOLFOX-4) in the patients with metastatic colorectal cancer (MCRC). A total of 120 patients with MCRC were randomly divided into the experimental group (FOLFOX-4 plus YZD, 60 cases) and the control group (FOLFOX-4 plus placebo, 60 cases), according to the sequence of hospitalization from January 2005 to December 2007. The treatment was supposed to be continued until disease progression (PD) or for 48 weeks (i.e., up to 24 cycles of FOLFOX-4). Response rate (RR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were observed. RR was 41.5% in the experimental group and 34.0% in the control group [odds ratio (OR): 1.18, 95% CI: 0.77 to 1.82, P=0.432]. Median PFS were 9.0 months and 8.0 months, respectively [hazard ratio (HR): 0.78, 95% CI: 0.53 to 1.15, P=0.215]. Median OS were 21.0 months and 18.0 months (HR: 0.65, 95% CI: 0.43 to 0.99, P=0.043) and grade 3/4 AEs were 56.6% and 76.7% (OR: 0.61, 95% CI: 0.18 to 0.87, P=0.020), respectively. YZD combined with FOLFOX-4 chemotherapy significantly improved OS in this first-line trial in the patients with MCRC and significantly decreased grade 3/4 AEs. However, RR was not improved, and PFS did not reach statistical significance by the addition of YZD. The treatment of YZD combined with FOLFOX-4 may be necessary in order to optimize efficacy and safety.

A pilot study of FOLFOX with or without radiation in treating patients with locally advanced rectal cancer.

e14147 Background: Preoperative 5FU-based chemo plus radiation therapy is standard for patients (pts) with locally advanced rectal cancer (RC). We conducted a pilot feasibility trial of adding the third generation drug oxaliplatin to the standard treatment to see whether the treatment outcome can be improved and the place of RT can be replaced. Methods: Pts with clinical stage II-III resectable RC were treated with 4 cycles of FOLFOX (CT) or 5 cycles of FOLFOX with radiation (2Gy/fraction, total 46Gy, CRT). Pts then were re-imaged and had repeat colonoscopy with MRI to assess the primary tumor response. Those with progressive disease in FOLFOX group were to be referred for pre-op 5FU plus RT, followed by surgery, and those with clinical regression/stable disease were to have surgery without pre-op RT. Post-op 5FU plus RT was planned for any pts who did not have an R0 resection. 7-8 cycles of FOLFOX were recommended in Post-op chemo. The primary endpoint was the objective response rate. Secondary outcomes were the pathologic CR rate, the 3-year disease free survival and local recurrence (LR) rate. Results: Of 51 pts were accrued since April 2007, 25 have completed pre-op RCT, 26 who have completed pre-op CT, 7 of 25 RCT pts (28%) had a path CR, however no pts with CT had path CR, the difference was significant. ORR was 92%, 80.8% and disease control rate (DCR) 96%, 96.2% respectively, there was no difference between the two groups. The quality of life was better and the in-hospital time was shorter the CT alone group. Local and distant recurrence rate data are immature. But so far, no recurrence was found in the CT group, which indicated the potential benefit of CT alone in the adjuvant setting. Conclusions: Preliminary results of this pilot trial depicts that preoperative FOLFOX alone without RT achieves a high rate of DCR. And FOLFOX with RT achieves a high rate of CR. Further phase III trials are warranted.

Phase II trial of five fractions of radiotherapy followed by four cycles of FOLFOX chemotherapy as preoperative therapy for rectal adenocarcinoma: Report of an interim response analysis.

e14003 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Multi-institution trials incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the known benefits of preoperative RT on local response/control, (2) provide for preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT, (4) keep the surgery within 4 weeks of where it would be with conventionally fractionated RT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed by a surgeon to be candidates for extirpative surgery, provided the response to preoperative treatment was sufficient. Preoperative treatment consisted of 5 fractions of pelvic RT (25 Gy to involved mesorectum, 20 Gy to elective nodes) followed by a 2 week rest, followed by 4 cycles of bi-weekly mFOLFOX6. Surgery was 4-9 weeks after completion of preoperative treatment. Postoperative CT was at the discretion of the treating medical oncologist, but another 6-8 cycles of FOLFOX was recommended. The principal objectives are to demonstrate that this regimen can achieve T stage down staging (ypT < cT) and acute grade 3+ gastrointestinal (GI) morbidity equal to or better than historical controls. Results: Accrual opened November 2009. To date 36 patients have enrolled, with 6 cases experiencing grade 3 acute GI morbidity. Twenty-five cases (all cT3, 18 cN+, 3cM1) have had sufficient time to proceed to surgery. Two were inevaluable: one withdrew consent prior to CT and one received no surgery due to progression of distant disease (with local response). Of the 23 evaluable cases, all had R0 resections, 18 (78%) had ypT0-2 residual disease (6 ypT0 (26%), 4 ypT1, 8 ypT2), 19 (83%) were ypN0. Conclusions: Interim analysis shows that 5 fractions of preoperative RT followed by 4 cycles of FOLFOX is effective in eliciting tumor response. This template preserves the known benefits of radiation therapy on local control while allowing incorporation of full-dose multi-agent chemotherapy.

Global clinical experience with adjuvant oxaliplatin/5-fluorouracil (5-FU)-based chemotherapy for colon cancer: ACCElox registry.

e14078 Background: The Adjuvant Colon Cancer with Eloxatin (oxaliplatin)/5-FU (ACCElox) Registry was established in 2006 to record treatment and outcome information for patients with colon cancer in the Asia-Pacific, Latin America, the Middle East and Africa. Methods: Data were collected on patient/disease characteristics, treatments, adverse events and outcomes at registry entry, before each treatment, at treatment discontinuation and 6, 12, 24 and 36 months post treatment. The primary objective was to assess how adjuvant oxaliplatin/5-FU-based regimens are used in clinical practice, versus approved regimens and the clinical-trial experience. Results: By May 2010, 1,548 evaluable patients had been recruited (1,315 [84.9%] of which were treated with FOLFOX [5-FU + leucovorin + oxaliplatin]: median age 58.2 years, range 18.2–89.2; 56.7% men; 72.7% stage III, 27.3% stage II colon cancer). The median number of cycles of FOLFOX received (based on oxaliplatin administration) was 12, which is in line with the recommended number. The median dose received of each component of the regimen over the treatment course closely reflected the recommended dose (Table). 69% (n=884) of patients receiving ≥2 cycles had a treatment delay of ≥4 days; among these, dose delays were mainly due to adverse events (43%, of which platelet, bleeding and clotting disorders=25% and white cell and reticuloendothelial disorders=65%) or personal convenience reasons (37%). The majority of patients completed the treatment course (n=985, 75%). Among those who discontinued treatment (n=328), physician/patient refusal (n=124, 38%) and adverse events (n=103, 31%) were the primary reasons. Conclusions: FOLFOX is the most common oxaliplatin/5-FU-based regimen used and appears to be applied in clinical practice in line with the approved regimen. Outcome data from this cohort will be reported at a later date. FOLFOX median (IQR) dose/cycle N (% of total, n = 1,315) Fluorouracil (mg/m2) Leucovorin (mg/m2) Oxaliplatin (mg/m2) Recommended dose/cycle — 2,400 400 85 Cycle 1 1,310 (99.6%) 2,000 400 85 4 1,238 (94.1%) 2,000 400 85 8 956 (72.7%) 2,000 400 85 12 745 (56.7%) 1,900 400 74

Was it worth it (WIWI)? Patient satisfaction with clinical trial participation: Results from North Central Cancer Treatment Group (NCCTG) phase III trial N0147.

6122 Background: Despite the potential therapeutic advantage, only approximately 5% of eligible adult cancer patients enter oncology clinical trials. Knowledge of whether patients thought the clinical trial experience was beneficial may provide insights for barriers to accrual and inform future trial design. A recent phase III study in stage III colon cancer, N0147, included the 5-item “Was It Worth It” (WIWI) patient questionnaire to assess patient satisfaction. We report the results here. Methods: Patients received 12 bi-weekly cycles of FOLFOX alone or with cetuximab. WIWI was completed at treatment discontinuation. Comparisons between groups for each WIWI item was carried out via Fisher’s exact tests. Results: WIWI data was provided by 1081 patients (see table). The majority said trial participation was worth it (95%), would do it again (90%), would recommend it to other people (95%), and that their QOL was improved by going on trial (65%). Over one-third of patients (37%) said their satisfaction was not related to their treatment outcome. Patients treated with Cmab were less likely to say participation was worth it and more likely to say their satisfaction was related to treatment outcome. Elderly patients were less likely to say trial participation was worth it, would do it again and would recommend it. FOLFOX-treated patients aged 70+ versus those aged <70 were more likely (76% vs 58%) to report that their satisfaction was related to their outcome (p=0.0001). Conclusions: In N0147, patients treated with Cmab and elderly patients indicated lower levels of satisfaction, due likely to the increased toxicity related to the Cmab treatment. Contrary to popular belief, patient satisfaction was not related to treatment outcome. Patient satisfaction can be assessed, is a sensitive measure to between-arm differences, and should be included in future randomized studies. Answered yes to . . . FOLFOX FOLFOX +Cmab P value Age <70 Age 70+ P value Worth it? 96% 94% 0.01 95% 92% 0.02 Do again? 93% 86% 0.0001 90% 84% 0.004 QOL improved? 67% 64% 0.13 66% 63% 0.32 Satisfaction level related to outcome? 60% 65% 0.05 60% 78% 0.0001 Recommend? 97% 94% 0.01 96% 92% 0.005

Effect of PSK on FOLFOX4-induced peripheral neuropathy and bone marrow suppression in patients with metastatic colorectal cancer.

596 Background: FOLFOX4 has been confirmed as an effective treatment for metastatic colorectal cancer and is used as a postoperative adjuvant therapy. However adverse effects such as cold-sensitive paresthesia and bone marrow suppression are common and may necessitate changes in chemotherapy regimen despite FOLFOX effectiveness. PSK, a polysaccharide derived from a species of mushroom, has been developed in Japan as an immune-enhancing agent and is widely used in patients with gastric, colorectal and pulmonary cancer. PSK has also been reported to decrease some adverse effects of chemotherapy. Methods: FOLFOX4 combined with PSK was administered to patients with metastatic colorectal cancer and the results were evaluated. Eight cycles of FOLFOX4 and PSK (3.0 g/day, p.o.) were given to 25 patients with metastatic colorectal cancer (19 hepatic, 3 pulmonary and 3 peritoneal). Results: No patients showed CR (complete response, 0%) while PR (partial response), SD (stable disease) and PD (progressive disease) were seen in 48%, 36% and 16% of patients, respectively. Response rate was 48% and disease control rate was 84%. Frequency of adverse effects was significantly lower than described in the published data. Grades 1 and 3 neutropenia occurred in 48% and 24% of patients, respectively; grades 1 and 3 nausea in 48% and 4%, respectively; and grades 1, 2 and 3 sensory neurotoxicity in 52%, 4% and 0%, respectively. No patient dropped out due to adverse effects in this study. Conclusions: PSK plus FOLFOX4 seems as effective as FOLFOX4 monotherapy, and significantly less toxic. These results suggest that this combination therapy may be more effective when given for a longer period, with lower incidence of adverse effects. No significant financial relationships to disclose.

Oxaliplatin-Free Interval as a Risk Factor for Hypersensitivity Reaction among Colorectal Cancer Patients Treated with FOLFOX

Background: Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood. Patients and Methods: Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed. Results: Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016). Conclusions: An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.

Predicting Adverse Outcomes After Complex Cancer Surgery

Predicting Adverse Outcomes After Complex Cancer Surgery

Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases

PurposeAdjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs.MethodsBetween 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS).ResultsBy the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group (P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group (P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15–0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083–0.86, P = 0.026) than 5-FU/LV-based.ConclusionsAdjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy.

Neoadjuvant FOLFOX-bev, without radiation, for locally advanced rectal cancer.

3511 Background: Preoperative 5FU-based chemo plus radiation therapy (RT) is standard for U.S. patients (pts) with locally advanced rectal cancer (RC). We conducted a pilot feasibility trial of pre-op FOLFOX-bevacizumab (bev) without RT for good-risk RC. Methods: Pts with clinical stage II-III RC (but not T4 tumors) who were candidates for sphincter-sparing surgery, were treated with 6 cycles of FOLFOX. Bev was included for cycles 1-4. Pts then were re-imaged and had repeat sigmoidoscopy with endorectal ultrasound (ERUS) performed by their surgeon to assess the primary tumor response. Those with stable/progressive disease were to be referred for pre-op 5FU plus RT, followed by surgery, and those with clinical regression were to have surgery without pre-op RT. Post-op 5FU plus RT was planned for any pts who did not have an R0 resection. Post-op chemo was left to investigator discretion, however 6 cycles of FOLFOX were recommended. The primary outcome was the R0 resection rate. Secondary outcomes were the pathologic CR rate, the 3-year disease free survival and local recurrence (LR) rate. Results: Of 31 pts accrued since March 2007, two were withdrawn from the study for cardiovascular toxicity (1 angina, 1 arrhythmia) after 1-2 cycles of FOLFOX-bev. Both had R0 resections. Of 29 who have completed pre-op chemo, all 29 had clinical regression and proceeded to surgery without pre-op RT. All 29 had R0 resections. Eight of 29 (27%) had a path CR. One pt with 14+ nodes and a close deep margin received post-op RT, and has since developed pulmonary mets. One pt with pathologic yT1N0 disease had high output ileostomy post-op but was discharged home in stable condition on day 10. He died suddenly 3 days later. Autopsy did not identify a cause. Local and distant recurrence rate data are immature; however thus far, there have been no LRs and 3 distant recurrences, all pulmonary. 26 patients remain alive and disease-free. Conclusions: Preliminary results of this pilot trial indicate that preoperative FOLFOX-bev chemo without RT achieves a high rate of R0 resections and path CRs in good risk RC. Further trials of non-RT-containing approaches are warranted. Supported by Genentech. No significant financial relationships to disclose.

Recovery of Liver Function After the Cessation of Preoperative Chemotherapy for Colorectal Liver Metastasis

Preoperative chemotherapy containing oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) causes histological liver injury and increases postoperative morbidity and mortality in patients with colorectal liver metastasis (CRLM). However, information on the aggravation of liver function and its reversibility is scarce. A total of 55 patients who underwent a hepatectomy after receiving FOLFOX and/or FOLFIRI were included in the present study. Indocyanine green tests were repeatedly performed before hepatectomy for monitoring the change of hepatic functional reserve. A significant decrement in the ICG R15 value was observed at 2-4weeks (12.9%, P=.04), 4-8weeks (11.4%, P=.01), and 8 or more weeks (11.1%, P=.006) after the last chemotherapy, compared with results documented within 2weeks (16.8%). However, no significant change was observed among the values obtained at 2-4weeks, 4-8weeks, and 8 or more weeks. The individual ICG R15 values at the beginning and end of the cessation period also improved from 17.7% to 11.6% (P=.001). Histological liver injury was associated with larger amounts of operative blood loss but not with morbidity. Neither liver failure nor mortality occurred in the present series. The hepatic functional reserve, represented by the ICG R15 value, improves during the period after chemotherapy cessation. The present study suggests that chemotherapy cessation for at least 2-4weeks enables an improvement in the hepatic functional reserve, especially among patients with an abnormal ICG R15 value (>10%) who have received 6 or more cycles of FOLFOX and/or FOLFIRI.

Adjuvant Chemoradiotherapy in Patients With Stage III or IV Radically Resected Gastric Cancer

Adjuvant chemoradiotherapy does not represent the standard of care in patients with resected high-risk gastric cancer; however, results from phase 2 and randomized trials suggest improvement in overall survival. We assessed the feasibility and toxic effects of chemoradiotherapy as adjuvant treatment in locally advanced gastric cancer. Pilot study. University hospital. Twenty-nine patients with T4N+ or any TN23 gastric cancer previously treated with potentially curative surgery were enrolled. All of the patients received combined adjuvant chemotherapy with FOLFOX-4 (ie, a combination of folinic acid [leucovorin], fluorouracil, and oxaliplatin [Eloxatin]) for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy was begun after the first 2 cycles of FOLFOX-4, which was reduced by 25% during the period of concomitant radiotherapy. Treatment toxic effects according to the National Cancer Institute-Common Toxicity Criteria classification, overall and disease-free survival rates, and identification of prognostic indicators. All of the patients completed treatment. Severe hematologic and gastrointestinal toxic effects occurred in 10% and 33%, respectively. No acute hepatic or renal toxic effects were observed; 1 patient experienced severe neurotoxicity. Disease-free and overall survival rates at 1, 2, and 3 years were 79%, 35%, and 35% and 85%, 62.6%, and 50.1%, respectively, and were shown to be substantially better than those observed in untreated patients. Long-term outcome was related to TNM stage, basal serum tumor marker level, and, particularly, lymph node ratio. A multimodal approach with FOLFOX-4 and radiotherapy is feasible and effective for the treatment of patients with resected high-risk gastric cancer.

Adjuvant FOLFOX-4 in patients with radically resected gastric cancer: Tolerability and prognostic factors

The aim of the present study was to evaluate the toxicity and efficacy of the FOLFOX-4 regimen as adjuvant chemotherapy in patients with gastric cancer after radical surgery. Fifty-four patients (1 stage Ib, 6 stage II, 22 stage IIIa, 14 stage IIIb and 11 stage IV) received 8-12 cycles of FOLFOX-4 (oxaliplatin 85 mg/m(2), Day 1; leucovorin 100 mg/m(2) i.v., Days 1 and 2; 5-fluorouracil 400 mg/m(2) i.v. bolus, Days 1 and 2 and 600 mg/m(2) in 22 h i.v. continuous infusion, Days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the National Cancer Institute Common Toxicity Criteria. Disease-free (DFS) and overall survival (OS) were calculated according to the Kaplan-Meier method. Thirty-eight patients (70.4%) completed the prescribed number of cycles of chemotherapy. The toxicity was mild. Grade 3-4 neutropenia occurred in 57% of patients, thrombocytopenia and anemia in 2% of cases. Peripheral neuropathy was experienced by 46% of the patients (grade 4 in 2% of cases). Five patients experienced grade 3 gastrointestinal toxicity. After a median follow-up of 33.1 months, 17 patients relapsed and 17 succumbed to the disease. The mean observed DFS and OS were 49.7 months (range 40.7-58.8) and 57.9 months (range 49.6-66.2), respectively. At univariate analysis, females and patients who had received <8 cycles of chemotherapy had a significantly worse probability of DFS and OS. The Cox model showed gender to be independent of the factors affecting DFS. Adjuvant FOLFOX-4 is feasible and well-tolerated in patients radically resected for gastric cancer. Receiving <4 months of adjuvant FOLFOX-4 could be detrimental to prognosis.