Safety Of Oxaliplatin Research Articles

A Phase II Study of Capecitabine plus Oxaliplatin as First-Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer

Objective: This study aimed at assessing the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX regimen) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC). Patients and Methods: Forty-six eligible patients aged ≧70 years with previously untreated AGC received oxaliplatin 130 mg/m² intravenously over a 2-hour period on day 1 plus oral capecitabine 850 mg/m² twice daily on days 1–14, every 3 weeks. Results: All patients were evaluable for toxicity and 45 patients for efficacy. A median of 6 cycles (range 1–8) was administered. The overall response rate was 48.9% (95% CI 34–64) with 1 complete response, 21 partial responses, 15 stable diseases and 8 progressions. Median time to progression was 6.0 months (95% CI 3.9–8.1), and the median overall survival was 10.0 months (95% CI 8.6–11.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (6.5%), thrombocytopenia (2.2%), nausea (2.2%), vomiting (4.3%), diarrhea (4.3%) as well as peripheral neuropathy (2.2%); grade 4 toxicities occurred in none of the patients. Conclusion: The XELOX regimen with capecitabine at a lower dose of 850 mg/m² is active, fairly tolerable and conveniently delivered as first-line chemotherapy for elderly AGC patients.

Comparative analysis of the efficacy and safety of chemotherapy with oxaliplatin plus fluorouracil/leucovorin between elderly patients over 65 years and younger patients with advanced gastric cancer

A chemotherapy regimen with oxaliplatin, fluorouracil, and leucovorin is commonly used to treat advanced gastric cancer (AGC). This study was designed to compare the efficacy and the safety of oxaliplatin plus fluorouracil/leucovorin administered biweekly (mFOLFOX6) between elderly patients aged over 65years and younger counterparts with AGC. This analysis included 82 AGC patients (≥65:31, <65:51). Patients with previously untreated chemo-naïve advanced adenocarcinoma of the stomach received oxaliplatin 85mg/m(2), 5-FU bolus 400mg/m(2) on day1 and 5-FU 1,500mg/m(2), leucovorin 75mg/m(2) 22h infusion on days1 and 2 every 2weeks. The aim of the study was to compare efficacy and safety, including response rate (RR), progression-free survival (PFS), overall survival, and grade ≥3 adverse events, between patients aged ≥65 years and patients aged <65 years. Median progression-free survival (PFS) was not significantly different between both groups (≥65: 5.8months, <65: 5.7months, respectively, HR 0.77, 95% CI: 0.44-1.16, P=0.18). Median overall survival was not significantly different between both groups (≥65: 10.3months, <65: 9.5months HR 0.83, 95% CI: 0.50-1.37, P=0.46). The rate of grade 3 or 4 neutropenia did not differ with age group (≥65: 51.6%, <65: 43.1%); nor did the rates of neutropenic fever (≥65: 16.1%, <65: 5.9%), and infection without neutropenia (≥65: 3.2%, <65: 3.9%). Rates of grade ≥3 toxicities such as thrombocytopenia, nausea/vomiting, or peripheral neuropathy were not significantly different between the two groups. mFOLFOX6 maintains its efficacy and safety in elderly patients aged over 65years in comparison with AGC patients aged <65 years. Its judicious use should be considered regardless of age.

Randomized controlled study of oxaliplatin combined with tegafur and calcium folinate in treatment of advanced gastric cancer

Objective To compare the efficacy and safety of oxaliplatin combined with tegafur and calcium folinate with FOLFOX4 regimens on patients with advanced gastric cancer. Methods 120 patients with advanced gastric cancer were randomly divided into two groups. concluding 60 cases in observation group (modified group) treated with oxaliplatin combined with tegafur and leucovorin and 60 cases in control group (FOLFOX4 group) treated with oxaliplatin combined with calcium folinate and fluorouracil. Clinical efficacy was evaluated after 2 (3-6) cycles. Results The clinical efficacy rates of observation group and control group were 63.3 ％ (38/60) and 41.7 ％ (25/60), respectively (x2 =5.647, P =0.028). The median progression-free survival and median overall survival of patients in observation group were 7.7 months and 11.6 months,respectively, and those in control group were 7.3 months and 10.1 months, respectively. The median progression-free survival (P =0.032) and median overall survival (P =0.005) were statistically significant differences. The increased ratio of Karnofsky score of patients in observation group was higher than that in control group (P =0.015). The incidence of myelosuppression in observation group was lower than that in control group (P =0.044). There was no significant difference between the two groups on other adverse reaction rates. Conclusion The efficacy and safety of oxaliplatin plus tegafur and leucovorin in the treatment of advanced gastric cancer is superior to FOLFOX4 regimen, and worthy of clinical application. Key words: Stomach neoplasms; Treatment outcome; Oxaliplatin; Tegafur, Calcium folinate

Efficacy and Safety of Oxaliplatin, 5-Fluorouracil, and Folinic Acid Combination Chemotherapy as First-Line Treatment in Metastatic or Recurrent Gastric Cancer

PurposeWe retrospectively determined the efficacy and safety of the combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer.Materials and MethodsBetween January 2006 and August 2009, 39 patients with histologically-confirmed, metastatic or recurrent gastric cancer underwent chemotherapy, and the results were retrospectively investigated. The chemotherapy regimen consisted of oxaliplatin (100 mg/m2) and FA (200 mg/m2; 2-hour infusion), then 5-FU (2,400 mg/m2; 46-hour continuous infusion) every 2 weeks.ResultsThirty-nine patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1 to 16). Of the 32 evaluable patients, zero patients achieved a complete response and 11 patients achieved a partial response (response rate, 28.2%). The median time-to-progression and overall survival were 4.3 months (95% confidence interval [CI], 2.0 to 6.5 months) and 9.8 months (95% CI, 3.5 to 16.0 months), respectively. The main hematologic toxicity was anemia, which was observed in 119 cycles (56.7%). Grade 3/4 neutropenia was observed in 32 cycles (15.2%). The main non-hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. No treatment-related deaths were reported.ConclusionThis study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.

Phase II trial of oxaliplatin plus oral capecitabine as first-line chemotherapy for patients with advanced gastric cancer

The efficacy of chemotherapy for advanced gastric cancer is now widely accepted. However, the survival advantage is small, and no internationally accepted standard regimen has emerged. The present study investigated the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX regimen) as first-line chemotherapy in previously untreated patients with advanced gastric cancer. Patients received intravenous oxaliplatin (130 mg/m2 over 2 h on day 1) plus oral capecitabine (1,000 mg/m2 twice daily on days 1-14). Treatments were repeated every 3 weeks. Seventy-four patients were enrolled in the study, median age was 61 years (range, 32-74); median follow-up was 13.2 months (range, 2-24.5). In total, 364 cycles of chemotherapy were delivered. Overall response rate was 62.2% (95% CI, 51.2-73.2), with 3 complete and 43 partial responses; median time to progression and overall survival were 5.9 (95% CI, 4.8-7.0) and 10.8 months (95% CI, 7.9-13.7), respectively. The most common hematological adverse event was anemia (67.6% of patients). Grade 3-4 neutropenia was observed in 5 patients. The most common nonhematological toxicities were neuropathy (64.9%), nausea/vomiting (48.6%), diarrhea (28.4%), and hand-foot syndrome (39.2%). Grade 3-4 toxicities were rare. There were no treatment-related deaths. The XELOX regimen was active and well-tolerated as first-line chemotherapy in patients with advanced gastric cancer.

The phase II study of efficacy and safety of oxaliplatin with doxorubicin in recurrent ovarian cancer (OC).

5087 Background: There is no current standard of salvage chemotherapy in recurrent OC. Oxaliplatin is an effective third generation platinum compound which has no complete cross-resistance with carboplatin or cisplatin in OC. The purpose of our study was to assess efficacy and tolerability of combination of oxaliplatin and doxorubicin in second-line chemotherapy of OC. Methods: In case of disease progression following first-line chemotherapy pts received second-line chemotherapy with oxaliplatin 130 mg/m2 and doxorubicin 50 mg/m2 q3w. Time to progression (TTP) was chosen as the primary end-point. Three investigator centers participated in the study. Results: Totally 29 pts were included in this study. Tumors were platinum-sensitive (PFI>12 m) in 5 (17.2%), partially platinum-sensitive (PFI>6 m) in 12 (41.4%), platinum-resistant (PFI<6 m) in 11 (38.0%) cases, in 1 (3.4%) case sensitivity of tumor to platinum was not known. Objective response rate was 55.1% (24.1% complete remissions and 31.0% partial remissions). The median TTP was 10.7 m. With the median f.-up of 14.8 m the median overall survival was not reached. 1-year overall survival was 89%. There were no statistically significant differences in response rate and TTP between platinum-sensitive and platinum-resistant cancers (p>0.05). The median number of cycles was 5 (range 2-6). Toxicity grade 3-4 per cycle included neutropenia 14.6%, febrile neutropenia 0.7%, thrombocytopenia 5.1%. Sensory neuropathy grade 1-2 and 3 was observed in 8 (27.6%) and 2 (1.4%) cases respectively. There were 5 cases of oxaliplatin dose reductions and 10 cases of doxorubicin dose reductions; 10 cycles of chemotherapy were delayed due to toxicity. Conclusions: The combination of oxaliplatin and doxorubicin showed promising efficacy in either platinum-sensitive or platinum-resistant recurrent OC. Tolerability of this regimen was acceptable.

Phase II study of oxaliplatin plus leucovorin and 5-fluorouracil in heavily pretreated metastatic breast cancer patients

The aim of this phase II study was to investigate the efficacy and safety of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) in metastatic breast cancer (MBC) patients heavily pretreated with anthracyclines, taxanes, vinorelbine, gemcitabine, and capecitabine. Sixty-two women who had received at least 3 above-mentioned drug classes were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1, LV 200 mg/m(2) as a 2-h infusion followed by bolus 5-FU 400 mg/m(2) on day 1, and a continuous infusion of 5-FU 1,200 mg/m(2) for 44 h. The median patient age was 52 years with a median of two involved organs, and the metastases were mostly in the lung (53.2%), lymph nodes (51.6%), and liver (45.2%). Patients had a median of three prior chemotherapy regimens. Forty-five patients (72.6%) had prior exposure to all 5 classes of drugs. Based on an intention-to-treat analysis, 60 patients were assessable for responses and 11 patients achieved a partial response (PR), giving an overall response rate (ORR) of 18.3%. Twenty-one (35%) patients had stable disease (SD), and of these, 8 achieved long SD (13.3%). The median progression-free survival (PFS) was 3 months, and the median overall survival (OS) was 10 months. Toxicity was mild to moderate with grade 3 or 4 neutropenia, thrombocytopenia, and neuropathy occurring in 14 (22.6%), 9 (14.5%), and 3 (4.8%) patients, respectively. The study demonstrated that the combination of oxaliplatin plus 5-FU/LV was a well-tolerated salvage regimen with moderate activity in patients with heavily pretreated MBC.

Phase II study of oxaliplatin, UFT, and leucovorin in patients with metastatic gastric cancer

The present study evaluated the efficacy and safety of oxaliplatin, UFT, and leucovorin in metastatic gastric cancer. Patients received intravenous oxaliplatin 130 mg/m(2) on day 1, followed by oral UFT capsules (350 mg/m(2) per day) and leucovorin tablets (90 mg/day), every 8 h, for 14 days, in a 3-week cycle. Twenty-three patients (61% with > or = 2 metastatic sites), median age of 60 years (range, 39-69 years) were entered. Based on intention-to-treat analysis, one complete response and seven partial responses were found, resulting in an overall response rate (RR) of 35% (95% confidence interval [CI], 16-54), a median time to progression of 4 months (95% CI, 0.5-7.5), and a median overall survival (OS) of 8 months (95% CI, 4.5-11.5). The 1-year survival rate was 26%. Three patients did not complete the first course of 2 weeks; 1 died suddenly on day 16 with fatal lung embolism; 1 had rapid progressive disease and 1 experienced gastric hemorrhage on day 15 - both these patients withdrew. In the 20 patients assessable for toxicity no grade 4 toxicity occurred, grade 3 toxicity consisted of anemia in 1, diarrhea in 2, and neurotoxicity in 3 patients. No hand-foot syndrome (HFS) occurred. Oxaliplatin is an effective drug in gastric cancer, but, as previously reported, its feasibility in combination with capecitabine is hampered due to combined hand-foot-based toxicity. The present phase II study of a combination of oxaliplatin with UFT and leucovorin appears to have efficacy and tolerability comparable to two other drug regimens used in gastric cancer, without the HFS problem.

Triweekly Oxaliplatin Plus Oral Capecitabine as First-Line Chemotherapy in Elderly Patients With Advanced Gastric Cancer

To investigate the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC). Forty-four previously untreated patients with AGC aged 70 or older participated in the study. They received oxaliplatin 130 mg/m(2) as 2-hour intravenous infusion on day 1 and oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14 every 3 weeks XELOX. All patients were assessable for toxicity and 41 patients for response. Median age was 75 years (range, 70-83). In total, 215 cycles of XELOX were delivered. The response rate according to Response Evaluation Criteria in Solid Tumors was 51.2% (95% confidence interval [CI]: 35.9%-66.5%), with 2 complete responses, 19 partial responses, 11 stable diseases, and 9 progressions. At 9.5 months median follow-up, median time to progression and overall survival were 5.6 (95% CI: 4.6-6.6) and 9.8 months (95% CI: 7.4-12.2), respectively. Toxicities were generally mild. Grades 3 to 4 adverse events included: neutropenia (6 patients, 13.6%), diarrhea (6 patients, 13.6%), thrombocytopenia (5 patients, 11.4%), hand-foot syndrome (4 patients, 9.1%), nausea and vomiting (2 patients, 4.5%), and anemia (1 patient, 2.3%). Neutropenic fever occurred in 2 patients. There was no treatment-related death. XELOX is active and well tolerated as first-line chemotherapy for elderly patients with AGC. Given its ease of administration, it represents a good therapeutic option in the elderly.

Phase II study of oxaliplatin combined with S-1 (SOX) as first-line therapy for patients with advanced gastric cancer (AGC)

4553 Background: Oral fluoropyrimidine S-1 is one of the standard 1st-line chemotherapy for patients with AGC in Japan, and oxaliplatin is active against AGC in combination with fluoropyrimidine. This study evaluates the efficacy and safety of oxaliplatin in combination with S-1 in AGC. Methods: Eligibility criteria were: pathologically confirmed AGC, no prior chemotherapy, age &gt; 20, measurable lesions, ECOG PS &lt; 2, adequate organ function, written informed consent. Oxaliplatin was administered intravenously at a dose of 100 mg/m2 on day 1, and S-1 was administered orally twice daily on days 1–14 at a dose of 80 mg/m2/day, repeated every three weeks. The primary endpoint was objective response with RECIST guidelines. The sample size of 52 patients has an 80% power to demonstrate a 60% response rate (RR) with a one-sided type I error of 2.5%. Results: Between Apr. and Dec. 2007, 55 patients were enrolled at 8 centers in Japan. 51 patients were assessable for efficacy and 54 were assessable for safety. Patient characteristics: male/female = 34/17; median age 63 (range 30–77); PS 0–1/2 = 50/1; diffuse type/intestinal type = 35/16; metastatic/recurrent = 47/4. Median cycles 6.5 (range: 1–16). Thirty patients achieved in PR, and RR was 58.8% (95%CI: 44.2–72.4). Disease control rate (CR+PR+SD) was 84.3% (43/51; 95%CI: 71.4–93.0). One patient received subsequent curative surgery and achieved pCR. Median progression free survival was 6.5 months (95%CI: 4.8–11.3). Median time to treatment failure was 4.8 months (95%CI: 4.0–5.6). Grade 3–4 major adverse reactions were neutropenia (22.2%), thrombocytopenia (13.0%), leucopenia (3.7%), anorexia (5.6%), nausea (1.9%), and sensory neuropathy (3.7%). No treatment-related death was observed. Conclusions: The SOX regimen was well-tolerated and showed promising activity. This regimen may become one of the standard chemotherapy for ACG. One-year overall survival rate will be present at the meeting. [Table: see text]

Second-Line Therapy in Refractory Pancreatic Cancer. Results of a Phase II Study

Background: This phase II trial investigated the efficacy and safety of oxaliplatin (O), 5-fluorouracil (5-FU), and folinic acid (FA) (OFF) as second-line treatment for patients with metastatic pancreatic adenocarcinoma after failure of first-line gemcitabine treatment. Patients and Methods: 37 patients with confirmed progressive disease on gemcitabine therapy were treated with OFF (O 85 mg/m² days 8, 22; FA 500 mg/m², followed by 5-FU 2,600mg/m² days 1, 8, 15, 22) every 6 weeks. Patients were treated on an outpatient basis and remained on treatment until disease progression. Results: All patients were assessable for toxicity and effectiveness. We observed moderate hematotoxicity, the most common non-hematologic toxicity was neurotoxicity. A total of 12 patients had grade 3 nonhematologic toxicities: nausea and vomiting (4 patients), reversible neurotoxicity (5 patients), and diarrhea (3 patients). No grade 4 toxicities were observed. Median time to progression was 12 (1–125) weeks. Survival in second line was 22 (4–326+) weeks. Overall disease control rate was 49% (complete remission = 3%; partial remission = 3%; stable disease > 12 weeks = 43%). Conclusions: This regimen is feasible and active with an acceptable toxicity profile; it can be safely administered in an outpatient setting. There is an urgent need for further investigation in phase III trials.

Vascular Endothelial Growth Factor plus Epidermal Growth Factor Receptor Dual Targeted Therapy in Metastatic Colorectal Cancer: Synergy or Antagonism?

There has been an intensive effort to develop novel therapies for the treatment of metastatic colorectal cancer (mCRC). The anti-epidermal growth factor receptor (EGFR) antibodies panitumumab and cetuximab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab have demonstrated clinical efficacy and acceptable toxicity in the treatment of mCRC as single agents or in combination with chemotherapy. Recent clinical trials have explored the efficacy and safety of treatment regimens incorporating chemotherapy in combination with bevacizumab and either panitumumab or cetuximab in patients with mCRC. Results from the BOND-2 trial, which investigated cetuximab, bevacizumab, and chemotherapy in mCRC, provided support for this therapeutic approach. Two large randomized phase 3 trials were initiated to evaluate firstline treatment of mCRC. The Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) study investigated the efficacy and safety of oxaliplatin- or irinotecan-based chemotherapy and bevacizumab with or without panitumumab; CAIRO2 assessed the efficacy and safety of capecitabine/oxaliplatin and bevacizumab with or without cetuximab. In both trials, the combination of bevacizumab, an EGFR-specific antibody, and chemotherapy in first-line treatment of mCRC was associated with increased toxicity and no improvement in patient outcome. These results suggest that these specific combinations should not be used in first-line mCRC outside investigational studies.

Gemcitabine combined with oxaliplatin in pretreated patients with malignant pleural mesothelioma: an observational study

BackgroundThe aim of this study was to investigate the efficacy and safety of oxaliplatin ± gemcitabine in patients with diffuse malignant pleural mesothelioma (MPM) pretreated with pemetrexed.MethodsThe study enrolled consecutive patients with relapsed MPM, all of them pretreated with a platin-pemetrexed-based chemotherapy. Oxaliplatin 80 mg/m2 was administered as monotherapy or in combination with gemcitabine 1000 mg/m2 given on day 1 and 8. Cycles were repeated every 21 days. The primary endpoints were response rate and disease control rate. Secondary endpoints included overall survival (OS), time to tumour progression (TTP), progression-free survival (PFS), time to treatment failure (TTF), and toxicity.ResultsBetween February 2005 and September 2007 29 patients (median age: 65.0 years, World Health Organisation (WHO) performance status: 0–3) were enrolled. The follow-up period encompassed 5.4 to 97.4 weeks (median: 24.3 weeks). Out of these 29 patients, 15 were treated in second, 10 in third, 3 in fourth and 1 in fifth line, respectively. The majority of the patients received the combination oxaliplatin and gemcitabine (n = 25 vs. 4; 86.2 vs. 13.8%).The median overall survival (OS) was 71.7 weeks (30.6–243.3 weeks), whereas survival from the start of oxaliplatin/gemcitabine-treatment was 24.3 weeks (5.4–97.3 weeks). Median time to tumour progression (TTP) was 9.3 weeks (3.0–67.6 weeks).Partial response (PR) was observed in 2 patients (6.9%), stable disease (SD) for at least three courses of treatment in 11 patients (37.9%). Thus, disease control rate was 44.8%, whereas 16 of 29 patients exhibited progressive disease (55.2%).The toxicity profile was favourable, with no WHO grade 4-toxicities, only few dose-reductions were performed due to non-symptomatic haematotoxicities (neutropenia, thrombopenia). Mild WHO grade 2 neurotoxicity was seen in 6 patients.ConclusionPemetrexed-pretreated patients with progressive MPM may benefit from a consecutive chemotherapy with oxaliplatin and gemcitabine without significant toxicity.

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

Oxaliplatin in combination with 5-fluorouracil (FU) in a 48-hour continuous infusion (CI) as first-line chemotherapy for elderly patients (pts) with metastatic colorectal cancer (mCRC). TTD phase II trial

4057 Background: We previously reported a 35% overall response rate (ORR) with 5-FU CI (TTD schedule without modulation) plus CPT-11 as first line therapy in elderly pts with mCRC (Sastre et al. J Clin Oncol 23; 3545–51, 2005). The present study was carried out also in elderly pts to determine the efficacy (ORR as primary endpoint) and safety of oxaliplatin in combination with the same 5-FU schedule. Methods: Pts >72 y. with histologically confirmed mCRC, measurable disease, ECOG < 0–2, no previous adjuvant oxaliplatin and no prior treatment for metastatic disease. Treatment: Oxaliplatin 85 mg/m2 plus 5-FU 3,000 mg/m2 as a 48-hour CI q2w until progressive disease, undesirable toxicity or consent withdrawal. Results: 134 pts were included and 129 (96%) were eligible. Median age: 76y (72–85), male/female: 63/37%, and ECOG 0/1/2: 42/53/5%. Main comorbidities were hypertension (44%), diabetes (17%) and EPOC (11%). Median No of metastatic locations was 1 (37% with > 2 sites) mainly located in liver (77%) and lung (29%). 21% of pts received previous adjuvant chemotherapy. Efficacy: On an ITT analysis of 129 pts, ORR and control disease (ORR+SD) were 52% and 80% respectively. With a median follow-up of 14 months, median progression free survival and overall survival were 9 and 16.2 months respectively. 48 pts (37%) received 2 or more lines of chemotherapy mainly based in CPT-11. Seven pts (5.4%) followed resection of liver metastasis, of which 5 were complete. Grades 3–4 toxicities included anemia (2%), asthenia (9%), neutropenia (17%), febrile neutropenia (2%), thrombocytopenia (5%), diarrhoea (11%), nausea/vomiting (5/4%) and neurotoxicity grade 3 (18%). There was one treatment related death (pneumonia). Conclusion: To our knowledge this is the largest phase II prospective study in elderly pts with mCRC. The schedule seems to be effective and compared favourably with those reported in the literature in this population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis

Efficacy and Safety of Oxaliplatin and Gemcitabine with Bevacizumab in Advanced Non-small Cell Lung Cancer

We conducted a multicenter phase II study to evaluate the efficacy and safety of oxaliplatin and gemcitabine with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Patients with chemotherapy-naive, nonsquamous, stage IIIB or IV NSCLC received gemcitabine 1000 mg/m on days 1 and 8, oxaliplatin 130 mg/m on day 1, and bevacizumab 15 mg/kg on day 1 every 21 days for 4 cycles. Patients with stable disease or response received maintenance bevacizumab every 3 weeks until progression. Primary end point was median time to progression (TTP). Nineteen of 44 eligible patients had partial response in the intent-to-treat analysis for an objective response rate of 43% (95% confidence interval [CI], 26.3-60.1%); 16 patients had stable disease for a disease control rate of 80% (95% CI, 72.0-87.0%). Median TTP was 5.5 months (95% CI, 3.8-6.9 months), which approached that seen in phase III studies. Median survival was 13.7 months (95% CI, 7.3-21.8 months). The most common grade 3 or 4 adverse events were hypertension (11%), neutropenia (9%), diarrhea (7%), dyspnea (7%), and thromboembolic events (7%). Pulmonary hemorrhage was not observed. The results of this phase II study suggest that oxaliplatin and gemcitabine with bevacizumab was active and reasonably well tolerated. Median TTP approached that in phase III studies. This combination represents another treatment option for advanced NSCLC.

A multicenter randomized phase II trail of Oxaliplatin in the patients with colorectal cancer

Objective To evaluate the efficacy and safety of Oxaliplatin in the patients with colorectal cancer.

Biweekly gemcitabine and oxaliplatin (GEMOX) in first-line metastatic or recurrent nasopharyngeal carcinoma (NPC)—An early report

6071 Background: This multicenter phase II study evaluated the activity &amp; safety of oxaliplatin (Ox), a 3rd generation platinum, in combination with gemcitabine (GEM) for the first time in the palliative setting for patients (pts) with undifferentiated/ poorly differentiated NPC. Methods: Pts with untreated metastatic (M1) or locoregionally recurrent (LR) NPC were treated with a biweekly ‘GEMOX’ regimen (D1: GEM, 1,000 mg/m2 at 10 mg/m2/min; D2: Ox, 100 mg/m2 over 2 hrs) for a max. of 12 cycles. Intrapatient dose escalation of GEM to 1,250 mg/m2 was allowed from cycle 2 onwards if no significant toxicity occurred in cycle 1. Response was assessed every 4 cycles (RECIST criteria). Results: 23 pts accrued before 31st July 06 were evaluated for toxicity &amp; response; cut-off date for data analysis was 15th Oct 06. The median age was 53 yrs (range 38–72); 19 were men, all had ECOG status of 0–1. At enrolment, 7 pts (29%) had M1 disease only, 3 (12%) pts had LR only, &amp; the rest both M1 &amp; LR. All 7 pts with only LR received radical radiotherapy (RT) at initial diagnosis. A median of 11 cycles (range 3–13) were administered. Best overall response rate was 52%, with 12 partial responses &amp; 11 stable diseases. The median duration of response was 7 months (range 0.8–15). Grade (gr) 3–4 hematological toxicities (CTCAE ver 3) included neutropenia in 7 pts (30%, only 1 pt had fever), thrombocytopenia in 5 pts (26%, 1 gr 4 case with mild gum bleeding). Gr 3–4 non-hematological toxicities included gr 3 diarrhoea in 2 pts, gr 4 Ox-related hypersensitivity reaction in 1 pt, gr 3 epistaxis in 2 pts. The commonest non-hematological toxicities were gr 1–2 Ox-related sensory neuropathy (22pts). There were no treatment-related deaths &amp; only 1 pt withdrew from study due to drug-related toxicity. Conclusions: GEMOX is a promising regimen among pts with metastatic &amp; recurrent NPC. Accrual is ongoing with a planned total sample of 40 pts. No significant financial relationships to disclose.

FOLFOX-4 Regimen as First-Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer: A Safety Study

Gastric cancer is often diagnosed in advanced stage (AGC) and in elderly patients. Current chemotherapies induce severe toxicity and are difficult to deliver. Some authors have shown the activity and safety of oxaliplatin with various 5-fluorouracil (FU) and leucovorin (LV) infusions in AGC. The aim of our study was to evaluate the feasibility of the FOLFOX-4 regimen in elderly patients with AGC. From 6/2003 to 7/2005, 33 patients (median age 74 years, range 66-79 years) were enrolled into the study. 31 patients were assessable for the safety analysis and for response. We recorded complete response in 4 patients (13%), partial response in 6 patients (19%), 9 (29%) stable disease and 12 progressive disease for an overall response rate of 32% (95% CI, 16% to 48%). At median follow-up of 20 months the median time to progression was 6.4 months. The therapy was well tolerated, the main G1/2 toxicities were nausea, vomiting and diarrhea. Only 2 patients suffered from severe vomiting. Severe hematologic toxicities were uncommon. Anemia G3 was recorded in 3 patients, neutropenia G3 in 6 patients and febrile neutropenia in 1 patient. G1 and G2 neurotoxicity were a common event while G3 sensorial neuropathy was not reported. We conclude that although our patients were elderly and most had a PS 2, the regimen was manageable, easy to deliver, well accepted by the patients and active.

Oxaliplatin as First-Line Treatment in Inoperable Biliary Tract Carcinoma

Background: A multicenter phase II study was conducted in order to evaluate the efficacy and safety of oxaliplatin as first-line treatment of patients with locally advanced or metastatic carcinoma of the biliary tract. Patients and Methods: Twenty-nine chemo-naïve patients with locally advanced or metastatic biliary tract carcinoma received oxaliplatin 130 mg/m² i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity. Results: An objective response (3 complete responses, 3 partial responses) was achieved in 6 patients (20.6%, 95% CI 5.95–35.4). Disease control (complete response, partial response and stable disease) was observed in 14 patients (48.2%). The median time to tumor progression was 3 months (range 0.7–39) and the median overall survival was 7 months (range 1–39). The 1-year survival rate was 32%. Toxicity was mild. Conclusion: Oxaliplatin is an active agent against biliary tract carcinoma and therefore should be further investigated in combination with other cytotoxic drugs.