Gemcitabine And Oxaliplatin Research Articles

Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: A large multicenter AGEO study

The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed. This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010. Survival curves were drawn with the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were used to evaluate prognostic factors. Two hundred four consecutive patients were treated with GEMOX (median age, 60 years; men, 86%; underlying cirrhosis, 76%). Grade 3-4 toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia 18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16% of the cases. The overall response and disease control rates were 22% (95% CI, 16-27) and 66% (95% CI, 59-72), respectively. No clinical or biological factors were associated with the treatment response, and 8.5% of the patients were subsequently eligible for curative-intent therapies after downstaging. Median PFS, TTP, and OS were 4.5 (95% CI, 4-6), 8 (95% CI, 6-11), and 11 months (95% CI, 9-14), respectively. In multivariate analysis, gender (p=0.03), underlying cirrhosis (p=0.01), CLIP score (p=0.03), and response to GEMOX (p<0.0001) were independently associated with OS. This large study confirms that GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor responses permitted potentially curative treatment that was not initially feasible in a significant proportion of patients.

Induction gemcitabine and oxaliplatin therapy followed by a twice‐weekly infusion of gemcitabine and concurrent external‐beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)). Patients without disease progression then received gemcitabine twice weekly (50 mg/m(2) daily) concurrent with radiotherapy (50.4 grays) and were re-evaluated for resectability. Thirty-nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow-up of 13 months, the median progression-free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation.

Phase Ib study of gemcitabine and oxaliplatin with erlotinib in patients with advanced biliary tract cancer.

e14503 Background: Gemcitabine (GEM) with a platinum agent such as oxaliplatin (OX) is standard therapy for advanced biliary tract cancers (ABTC). The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has also shown modest benefit in ABTC. Erlotinib (E) induces G1/S cell cycle arrest and may exhibit sequence-specific synergy with GEM. Given continuously, it may antagonize the action of chemotherapy against cycling tumor cells but intermittent pulsatile dosing of EGFR TKIs in combination with chemotherapy may lead to maximum efficacy. The purpose of this study is to assess the tolerability of E when pulsed with GEM and OX (GEMOX). Methods: This investigator initiated, single institution phase Ib study (NCT00987766) used a standard 3+3 dose-escalation model in patients with ABTC, pancreas cancer or duodenal cancer. The primary endpoint was to evaluate the maximum tolerated dose (MTD) of pulsatile E in combination with GEMOX. Patients received escalating doses of E starting at 50 mg daily (given on D3-8) with GEM on D1 (dose rate 10 mg/m2/min) and OX on D2 every two weeks. Dose-limiting toxicity was defined as any treatment-related, first course (28 days) non-hematologic ≥Gr3 toxicity, except nausea/vomiting or Gr4 hematologic toxicity. Results: Nineteen patients have been enrolled and 4 dose levels have been explored. Two of two patients experienced DLT [Gr3 diarrhea (n=1), Gr4 anemia (n=1)] at a dose of 150 mg E + 1000 mg/m2 GEM + 85 mg/m2 OX, exceeding the MTD. Most frequent toxicities were nausea (68%), neuropathy (68%), fatigue (63%) diarrhea (52%) and rash (52%), most Gr1 or 2. Disease stabilization occurred in 12/17 (71%) evaluable patients (5/9 ABTC, 7/8 pancreas), and partial responses were seen in 4/17 evaluable patients (24%), all with ABTC (4/9). The rate of progression-free survival at 6 months was 75% in ABTC. Conclusions: The MTD and recommended phase 2 dose of E in combination with GEMOX was E 150 mg given on days 3-8 with GEM 800 mg/m2 and OX 85 mg/m2 in this population. Clinical activity of this combination was seen in the majority of patients. An expansion cohort of an additional ten patients with ABTC at the MTD is ongoing, and correlative studies on available tissue will be performed.

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, &lt;40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

The clinical observation on the effect of gemcitabine plus oxaliplatin in treatment of relapsed or refractory non-Hodgkin's lymphoma

Objective To analyze the clinical efficacy of gemcitabine plus oxaliplatin in treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL).Methods 39 cases with relapsed or refractory NHL were treated by gemcitabine and oxaliplatin combination chemotherapy. After three cycles, its efficacy and adverse reactions were observed. Serum lactate dehydrogenase(LDH) concentration was detected before and after treatment and all the patients were followed up. Results The rate CR was 11cases (28. 1％ ), PR 16cases (41.03％), NC 7cases (17.95％),PD 5cases(12.82％).Thetotalresponserate(CR+PR) was 69. 23％. Conclusion Gemcitabineand oxaliplatin combination chemotherapy in treatment of patients with relapsed or refractory NHL was safe and effective. Key words: Lymphoma, non-hodgkin's; Gemcitabine; Oxaliplatin

Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial

The gemcitabine and oxaliplatin (GEMOX) has yielded among the longest progression-free survival durations in patients with advanced pancreatic cancer (APC). We postulated that adding bevacizumab would increase the effectiveness of GEMOX. Eligible patients had stage III or IV pancreatic cancer, ECOG PS 0-2, and no prior gemcitabine. Treatment included 1,000 mg/m(2) intravenous gemcitabine over 100 min on day 1, 10 mg/kg intravenous bevacizumab on day 1, and 100 mg/m(2) oxaliplatin given on day 2. Cycles were repeated every 2 weeks. CT imaging was performed every 6 weeks. Fifty patients were enrolled: 14 had stage III disease, the remainder stage IV. Median age was 59 years. Fourty-five patients were ECOG 0-1. The grade 3-4 toxicity rate was 94%; fatigue (47%) and nausea (40%) were frequent. One patient died after a bowel perforation; a second died of a CVA. The median PFS was 4.9 months; median survival was 11.9 months; 1 year survival was 42%. Locally advanced patients lived 12.8 months; metastatic patients lived 10.2 months. Patients developing grade 3 hypertension were more likely to have a radiologic response (P = .012); survival among the top and bottom quintiles of hypertension was 14.7 and 6.2 months, respectively. Survival correlated with baseline CA 19-9 (P = .004) and radiologic response. The overall response rate was 36%; 34% demonstrated stable disease. The GEMOX/bevacizumab regimen demonstrated an excellent median overall survival but did not meet our objective of a 14 month median survival. Toxicity was significant. We do not recommend further evaluation of this regimen.

A Phase III Randomized Trial of Gemcitabine–Oxaliplatin versus Carboplatin–Paclitaxel as First-Line Therapy in Patients with Advanced Non-small Cell Lung Cancer

This phase III study compared the efficacy and tolerability of gemcitabine and oxaliplatin (GEMOX) with paclitaxel and carboplatin (PCb) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer. Patients aged 18 years or older were randomized to PCb (paclitaxel 225 mg/m followed by carboplatin area under the curve = 6 on day 1 every 3 weeks) or GEMOX (gemcitabine 1,000 mg/m on days 1 and 8 followed by oxaliplatin 130 mg/m on day 1 every 3 weeks) for up to six cycles. The primary end point was progression-free survival (PFS), with tumor response rate, overall survival (OS), and quality of life as secondary end points. : The study was terminated after 383 patients had been randomized (371 received treatment) as the incidence of adverse events had exceeded the protocol-specified safety threshold (≥ 20% in either arm). No formal statistical comparisons were conducted. Median PFS was 4.44 months and 4.67 months in the GEMOX and PCb groups, respectively. Objective response rates (complete or partial) were 15.2% and 22.4% in the GEMOX and PCb arms, respectively. Median OS was 9.90 months (GEMOX) and 9.24 months (PCb); post hoc analyses showed median OS in patients aged 70 years or older to be similar to those younger than 70 years. PFS was similar in both groups of patients with adenocarcinoma histology, although OS favored the GEMOX group. Quality of life was improved from baseline in both groups. Toxicity profiles were comparable between the groups. PFS, OS, and objective response rates with GEMOX were similar to PCb. Nevertheless, toxicities limit the adoption of this regimen for routine use in advanced non-small cell lung cancer.

Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study

Patients with biliary tract cancer have a poor prognosis, and, until recently, no standard palliative chemotherapy has been defined. We aimed to investigate the efficacy and safety of cetuximab in combination with gemcitabine and oxaliplatin (GEMOX) for first-line treatment of biliary tract cancer. From Oct 1, 2006, to July 26, 2008, patients with unresectable locally advanced or metastatic biliary tract cancer were sequentially enrolled and treated at one centre in Austria. All patients received intravenous infusions of 500 mg/m(2) cetuximab on day 1, 1000 mg/m(2) gemcitabine on day 1, and 100 mg/m(2) oxaliplatin on day 2, every 2 weeks for 12 cycles. The primary outcome was overall response rate. Analysis was by intention to treat. Adverse reactions were assessed according to National Cancer Institute Common Toxicity Criteria. The study is completed and registered with ClinicalTrials.gov, number NCT01216345. 30 patients with median age of 68 years (IQR 62-73) were enrolled and included in the analysis. Objective response occurred in 19 patients (63%; 95% CI 56·2-69·8), of whom three (10%; 3·2-16·8) achieved complete response, and 16 (53%; 46·2-59·8) achieved partial response. Nine patients underwent potentially curative secondary resection after major response to therapy. Grade 3 adverse events were recorded in 13 patients: skin rash (n=4), peripheral neuropathy (n=4), thrombocytopenia (n=3), nausea (n=1), diarrhoea (n=1), and neutropenia (n=1); no grade 4 adverse events were recorded. Cetuximab plus GEMOX was well tolerated and had encouraging antitumour activity, leading to secondary resection in a third of patients. These findings warrant further study of cetuximab plus GEMOX in a large randomised trial.

Long term outcome in patients with cisplatin-refractory or multiply relapsed germ cell tumors following treatment with gemcitabine and oxaliplatin ± paclitaxel.

4585 Background: Patients (pts) with cisplatin-refractory or multiply relapsed germ cell tumors (GCT) have a poor prognosis and rarely achieve long term survival. Different combination chemotherapy regimens (CTX) including gemcitabine, oxaliplatin and paclitaxel have shown efficacy in these pts with resonse rates of 20-40 % and complete responses in 5-15%. However, long term survival appears to be rare and most studies have only been reported with short follow up. We here report long-term outcome from two previously reported trials. Methods: Two phase II trials have previously evaluated CTX with gemcitabine and oxaliplatin (GO) or GO plus paclitaxel (GOP) including a total of 76 pts (GO 35 pts / GOP 41 pts) (Kollmannsberger 2004; Bokemeyer 2008). A total of 26 patients were alive at the time of reporting of the studies, with 9 pts (12%) being in free of disease after CTX ± surgery and 17 alive with disease. Of the 9 pts free of disease 3 (3/35; 9%) and 6 (6/41; 15%) had received GO and GOP, respectively. Results: After a median follow up of 16 months (2 – 64+) for the 26 pts still alive, 8 (8/76; 11%) pts remain disease free with a median progression free and overall survival time of 32 months (11 – 64+) and 35 months [11-64+], respectively: 1/35 pts (3%) after GO and 7/41 pts (17%) after GOP. Another 3 pts, one after GO and 2 after GOP, who had relapsed after one, two and 6 months, achieved a complete remission after salvage treatment with CTX + surgery resulting in an overall long term survival rate of 13% (10/76 pts): 6% (2/35) after GO and 20% (8/41) after GOP. 2/10 pts had been absolutely refractory to previous cisplatin-based CTX. Eight pts have been now disease free for > 2 years after GO/GOP treatment, indicating potential long term cure in these heavily pretreated pts. Conclusions: Long term survival can be achieved with GO or GOP CTX in about 15% of pts with cisplatin-refractory or multiply relapsed GCT. Based on this retrospective analysis, the triple CTX combination GOP appears to achieve higher long term survival rates than two drug combinations. This finding requires confirmation in a randomized trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly, sanofi-aventis

Potential activity and safety of gemcitabine and oxaliplatin (GEMOX) in different histologic subtypes of advanced thyroid cancer.

e16011 Background: Patients with advanced, incurable thyroid cancer have few satisfactory therapeutic options. In this present study we assessed the activity and safety of the association of gemcitabine and oxaliplatin (gemox) in patients with different histology of advanced thyroid cancer refractory to I-131 treatment. Methods: Twelve patients with advanced thyroid cancer (4 papillary, 6 vesicular, and 2 mixed) were evaluated from our specialized hospital. All were refractory to I-131 treatment with a median age of 64 years. All patients received a combination of gemcitabine (1,000 mg/m2) + oxaliplatin (100 mg/m2) every two weeks until progression, limiting toxicity or a plained stop at 12 cycles. The response was evaluated by Response Evaluation Criteria in Solid Tumors after 4 cycles. Results: At this time, twelve patients were evaluated over our series. Complete and partial responses were observed in 1 and 5 patients respectively, yielding an ORR of 50%. Stable disease was reported in another 4 patients (33%). Objective responses were noted in 83 % (5 out of 6) vesicular subtypes. This combination was generally well tolerated, no grade IV toxicity was observed. The most common treatment-related adverse event being asthenia (n = 10 with 3 grade III), peripheral neuropathy (n=11 with 1 grade III), diarrhea (n=1), anemia (n=12), thrombopenia (n=5), neutropenia (n=4 with 1grade III). There was no toxic death related to the treatment. Conclusions: The GEMOX regimen remains effective and well tolerated in advanced differentiated thyroid cancer. thus, further evaluation of this new combination seems warranted and will be presented. No significant financial relationships to disclose.

Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([(18)F]FDG)-PET correlate with clinical outcome. Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m(2) (10 mg/m(2) per min) and oxaliplatin 85 mg/m(2) (2-h infusion). [(18)F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231. 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7.0 months (95% CI 5.3-10.3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [(18)F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUV(max)) after two cycles of treatment (5.72 [SD 2.01] at baseline; 3.73 [SD 1.88] after two cycles; p<0.0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, -2.80 [SD 1.95] vs five patients, 1.41 [SD 3.13]; p=0.009). Change in SUV(max) was a significant predictor of PFS (HR 1.35, 1.14-1.60, p=0.0006) and overall survival (1.25, 1.05-1.50, p=0.01). GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUV(max) on [(18)F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Genentech Oncology and Sanofi-Aventis.

Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II trial

Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months in patients with biliary tract cancers (BTCs). The aim of this study was to evaluate the efficacy and safety of the combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) in patients with BTCs including gall bladder cancer. We carried out a nationwide multicenter phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTCs received gemcitabine 1,000 mg/m(2) (day 1 and 8) and oxaliplatin 100 mg/m(2) (day 1), every 3 weeks. Fifty-three patients were evaluated, 60% had cholangiocarcinoma and the remaining 40% gall bladder cancer; the objective response rate was 18.9% (10/53 patients including 1 Complete response) [14.9%; 95% confidence interval (CI), 7.4-25.7%] in the treated population. Stable disease were observed in 27/53 (50.9%) patients, disease control rate was achieved in 69.8% of all patients. Median progression-free survival was 4.8 months (3.1-6.5, 95% CI) and median overall survival was 8.3 months (5.8-10.8, 95% CI). Grade 3/4 toxicities included neutropenia (33.9% of patients) and thrombocytopenia (7.6%). The GEMOX regimen demonstrated a modest antitumor activity and is well tolerated in patients with advanced BTCs.

A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: Interim analysis of the BINGO trial

4520 Background: There is no standard regimen for palliative chemotherapy of advanced biliary cancers. The GEMOX regimen is an option (BJC 2008). EGFR over-expression has been observed in advanced biliary cancers suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with advanced biliary cancer, WHO performance status 0–1, and without prior palliative chemotherapy were eligible for this international, open-label, two-stage, randomized phase II trial. Patients received GEMOX (gemcitabine, 1000 mg/m2 [10 mg/m2/min] at day [D]1; oxaliplatin, 100 mg/m2 at D2) alone (arm A) or with cetuximab (500 mg/m2 at D1 or 2, arm B), every 2 weeks. Randomization was stratified according to tumor stage and location, center, and prior treatments. The primary endpoint was 4-month crude progression-free survival (PFS) rate (H0 hypothesis, &lt; 40%; H1, ≥ 60%; planned sample size, 50 patients per arm). Secondary endpoints were response rate, PFS, overall survival, toxicity, early response assessment by PET, and blood/tumor EGFR signalling pathway member analyses. A data safety monitoring board-approved interim analysis was performed at the end of the first stage (18 patients per arm, minimal follow- up 4 months). Results: From October 2007 to October 2008, we enrolled 101 patients (median age, 62 yrs; male, 60%; metastatic, 86%; non-gallbladder, 76%). Among the 36 patients at the time of the interim analysis, the median number of treatment cycles was 6 and 8 in arms A and B, respectively. 76% (arm A) and 67% (arm B) had NCI-CTC grade 3–4 toxicity, mainly cytopenia (41%/39%), peripheral neuropathy (modified Levi's scale grade 2–3: 29%/33%), fatigue (6%/22%), gastrointestinal toxicity (12%/17%), and rash/hypersensitivity (0%/17%). The 4-month PFS rate was 44% (95% CI, 20–70) and 61% (95% CI, 36–83) in arms A and B, respectively. Conclusions: The GEMOX-cetuximab regimen seems well tolerated in patients with advanced biliary cancer. Adding cetuximab to GEMOX showed promising activity and therefore the trial was continued. Updated results on the whole population for primary and secondary endpoints will be available at the meeting. [Table: see text]

Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study

Advanced biliary tract carcinomas (BTCs) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) has shown promising activity in this setting. This international phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTC received gemcitabine 1000 mg m−2 (day 1) and oxaliplatin 100 mg m−2 (day 2), every 2 weeks. Seventy patients were enroled; 72.9% had metastatic disease. Sixty-seven patients were treated. There were 10 confirmed partial responses (14.9%; 95% confidence interval (CI), 7.4–25.7%) in the treated population (RECIST). Twenty-four patients (35.8 %) had stable disease. The objective response rate was 20.5% in patients with non-gallbladder cancers (9/44 patients) and 4.3% in patients with gallbladder cancers (1/23). Median overall survival for the intent-to-treat population was 8.8 months (95% CI, 6.9–11.1%) and progression-free survival was 3.4 months (95% CI, 2.5–4.6%). Grade 3/4 toxicities included thrombocytopenia (14.9% of patients), alanine aminotransferase elevation (13.4%), anaemia (10.4%), neutropenia (11.9%) and pain (11.9%). In this study, GEMOX demonstrated activity in non-gallbladder carcinoma, but poor activity in gallbladder carcinoma. GEMOX is well tolerated in advanced BTCs.

Gemcitabine and oxaliplatin (GEMOX), a promissing combination for the treatment of relapsed, advanced or metastatic non small cell lung cancer (NSCLC)

19061 Background: Combination of Gemcitabine and Oxaliplatin (GEMOX) given every 3 weeks was reported to be safe and active in phase II studies in first and second line therapy of NSCLC. The aim of our trial was to assess the efficacy and safety of oxaliplatin in combination with fixed rate infusion gemcitabine in the second and third line treatment of NSCLC, and to assess quality of life (QOL). Methods: 30 patients with advanced NSCLC, with Performance status (PS) ECOG 0–1, and who had failed first or second line treatment with chemotherapy and/or tyrosine kinase inhibitors were treated with GEM 1,000 mg/m2 over 100 min in combination with O× 100 mg/m2 over 2 hours both given on days 1 and 15 of each 28-day cycle. Primary endpoint was ORR and secondary endpoints were toxicity, time to tumor progression, time to treatment failure, overall survival. QOL was assessed by the FACT-L V.4 and Lung Cancer Subscale (LCS) questionnaires. Results: From the 30 patients, 16 (53%) were males and 14 (47%) females. 20 patients were Hispanics (66%), 7 Caucasian (23%), 3 African American (10%). Median age was 56 years. PS was ECOG 0 and 1 in 14(47%) and 16(53%) respectively. Histological subtypes were adenocarcinoma in 14 patients (47%), adeno-squamos in 1(3%), squamos in 3(1%), Bronchoalveolar carcinoma in 2 (6%) and unspecified in 9 (30%) patients. The treatment was second line for 22 (73%) patients and third line for 7(23%) patients. 1 patient progressed quickly and became ineligible for the treatment after enrollment. Two patients died on study from disease progression leading to respiratory and multi-organ failure. Partial responses were achieved in 4 (13%) patients, stable disease in 12 (40%) and progressive disease in 12 (40%). Grade 3/4 adverse events were seen in <10% of the patients and included fatigue, dyspnea, anemia and multiorgan failure (1 patient). There was a 25% improvement in the QOL LCS score. Conclusion: GEMOX combination given in day 1 and 15 of every 4 weeks shows activity and tolerable side effects when used to treat patients with advanced NSCLC who have previously failed chemotherapy, tirosine kinase or angiogenesis inhibitors, with a suggestion of QOL improvement. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology, sanofi-aventis sanofi-aventis

Two-weekly gemcitabine fixed dose rate and oxaliplatin combination chemotherapy for advanced non-small-cell lung cancer

Combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) is active in patients with advanced non-small-cell lung cancer (NSCLC). Oxaliplatin has a favourable toxicity profile compared to cisplatin. Gemcitabine's cellular uptake mechanism is saturable and fixed dose rate (FDR) infusion results in higher intracellular concentrations. We evaluated the feasibility, response rate and toxicity of bi-weekly GEMOX. Eligible patients with inoperable stage IIIB and IV NSCLC were treated with gemcitabine 1200mg/m(2) FDR and oxaliplatin 85mg/m(2), both given on d1 and d15 every 4 weeks for a maximum of six cycles. Tumour response was assessed every 8 weeks using RECIST criteria. Forty eligible patients initiated treatment between December 2002 and December 2004. There were nine partial responses (23%). An additional 23 patients (58%) had stable disease, resulting in a disease stabilization rate of 81%. The time to progression was 7.3 months (95% CI, 6.0-8.2 months). Median survival time was 10.4 months (95% CI, 8.7-13.2 months). The 1 and 2-year survival rates were 42% and 12%, respectively. The time to treatment response was 2.2 months (95% CI, 1.8-3.5 months) with a median response duration of 4 months. The most common grade 3 or higher toxicities were leucopenia (20%), asthenia (15%) and neurotoxicity (10%). There were no treatment-related deaths. Patients with performance status (PS) of 0 had a significantly longer survival than patients with higher PS (12.9 months versus 9.4 months, HR 0.45, P=0.03). Bi-weekly GEMOX is active and well tolerated for chemotherapy-naïve patients with advanced NSCLC. This regimen merits consideration for further investigation.

Concomitant Administration of Weekly Oxaliplatin, Fluorouracil Continuous Infusion, and Radiotherapy After 2 Months of Gemcitabine and Oxaliplatin Induction in Patients With Locally Advanced Pancreatic Cancer: A Groupe Coordinateur Multidisciplinaire en Oncologie Phase II Study

According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy. Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m(2) FU as a continuous infusion and 60 mg/m(2)of oxaliplatin weekly. Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%). Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.

Pseudocirrhosis in a pancreatic cancer patient with liver metastases: A case report of complete resolution of pseudocirrhosis with an early recognition and management

We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above-mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity as early recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.

Successful amelioration of oxaliplatin-induced hyperexcitability syndrome with the antiepileptic pregabalin in a patient with pancreatic cancer

Oxaliplatin, a platinum derivative used in the treatment of gastrointestinal cancers, has been associated with sensory neuropathies and, more infrequently, a neuromyotonia-like hyperexcitability syndrome. We present a case of hyperexcitability syndrome that developed during the treatment of pancreatic cancer with oxaliplatin and gemcitabine (GEMOX) that was successfully treated with pregabalin. A 54-year-old woman was undergoing chemotherapy with gemcitabine and oxaliplatin (GEMOX) for stage II-B pancreatic adenocarcinoma. On the third day of her fourth cycle, she presented with twitching of eyelids and tremors of hands. This twitching started bilaterally on the eyelids, followed by teeth jittering, hand shaking, and slurring of speech. A thorough neurological exam revealed no abnormalities except increased tone of both hands-she had difficulty opening her hand after closing it for a hand-grip. She was given a dose of 1 g of IV magnesium sulfate and 1 g of IV calcium gluconate, and 50 mg of IV diphenhydramine. In addition to reassurance, pregabalin was prescribed for these myotonic symptoms at a dosage of 50 mg by mouth three times daily. Improvement occurred in these symptoms within 12 h and she was almost asymptomatic within 72 h. Oxaliplatin causes a unique spectrum of acute neurological toxicities that have not been observed in patients receiving either cisplatin or carboplatin. Clinically, sensory alterations are most prominent, particularly cold-induced and perioral paresthesias. Other symptoms, such as cramps, jaw stiffness, voice changes, ptosis, and visual field changes suggest that motor nerves or muscles may also be involved (hyperexcitability). Hyperexcitability syndrome, distinct from cold-induced paresthesias and sensory neuropathy, is a rare complication of oxaliplatin chemotherapy; and up to date no pharmacotherapy has been successful in treating these symptoms. This is the first report of the successful amelioration of this syndrome with the antiepileptic pregabalin.

GEMOX as first-line chemotherapy in advanced pancreatic cancer (APC): A monoinstitutional experience

15179 Background: To date, gemcitabine (GEM) remains the cornerstone of chemotherapy (CHT) for APC. According to GERCOR and GISCAD phase III trials the combination of GEM and oxaliplatin (GEMOX) has proven superior to GEM alone in terms of response rate (RR), time to progression (TTP) and clinical benefit rate (CBR). Methods: We conducted a retrospective analysis on 19 patients (pts) affected with histologically-confirmed APC, in order to determine the impact of GEMOX as first-line chemotherapy in terms of objective responses (OR) and TTP, using the Kaplan-Meier method. Among the 19 pts considered there were 15 males and 4 females (median age at diagnosis of 60.84 yrs; ECOG 0–2). The staging, according to AJCC criteria, was: IIB in 1 case, III in 5 cases and IV in the 13 remaning cases. The only metastatic site was the liver (in 13/19 pts). Ten of the 19 pts underwent surgical treatment prior to CHT: 2 radically resected (R0) subsequently treated with GEMOX after recurrence, 4 with positive margins (R1) and 4 surgically palliated. All pts received GEM 1000 mg/m2/d1 + oxaliplatin 100 mg/m2/d2 every 2 weeks. The median number of cycles was 5.89. Results: Among the 19 pts, 3 had a partial response (PR, 15.69%), 6 had stable disease (SD, 31.57%); no complete response was observed and 10 pts had progressive disease (PD, 52.63%). The overall disease control rate (DCR: PR + SD) was 47.37% while the OR were 15.69%. The median survival observed was 9.03 months (95% C.I. 5.15–12.91) and the median TTP was 6.13 months (95% C.I. 2.81–9.46). The main toxicities were: leucopenia, piastrinopenia, diarrhoea, nausea, fever and peripheral neuropathy; 3 pts discontinued the treatment due to grade 3–4 neurotoxicity. Conclusions: In our experience GEMOX gives an improved control of APC in terms of OR and TTP, with acceptable toxicity. The OS is in accordance to literature as well as the other data. No significant financial relationships to disclose.