Safety Of XELOX Research Articles

Efficacy and Safety of Xelox in Comparison with Folfox in Metastatic Colorectal Cancer

Background: The study aimed to evaluate efficacy and safety of Xelox in comparison to Folfox chemotherapy for metastatic colorectal cancer. Methods: A quasi experimental study was undertaken at the Department of Oncology, Jinnah Postgraduate Medical Center between April 2022 to November 2022. All the patients coming to oncology department JPMC with confirmed diagnosis of metastatic colorectal cancer of age 18 years and above were included. All data were recorded in a predefined proforma by the researchers. Patients’ age, gender, and comorbidity, family history, and clinical characteristics were noted. The primary endpoints were the overall response rates and the frequency of adverse effects. Results: A total of 200 patients were enrolled with a mean age of 40 ± 14.38 years. There were 100 participants in the Xelox group while 100 participants in the Folfox group. About 45 (45%) in the Xelox group and 62 (62%) in the Folfox group reported adverse effects of the chemotherapy (p=0.015). The rate of neutropenia grade III/IV was greater in the Folfox category than the Xelox. Hand foot syndrome was significantly more frequently reported in the Xelox group than the Folfox group 22 (48.89%) and 18 (29.03%); p=0.036, respectively. Oral mucositis was also more frequently reported in patients taking Xelox than Folfox [20 (44.44%) vs. 15 (24.19%); p=0.023]. There was no significant statistical difference between Xelox and Folfox in terms of patient overall response rates. Conclusion: According to the study, there are no appreciable differences between Xelox and Folfox chemotherapy in terms of overall response rates among patients with colorectal cancer. However, overall, patients taking Folfox reported significantly higher rates of adverse effects with the exception of hand foot syndrome and oral mucositis which was more frequent in the Xelox group. Keywords: colorectal carcinoma, chemotherapy, xelox, folfox, Capecitabine, Oxaliplatin, fluorouracil

A prospective study of XELOX plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer (KSCC 0902)

BackgroundThis study was designed to evaluate the efficacy and safety of XELOX plus bevacizumab in a Japanese metastatic colorectal cancer population that included elderly patients.MethodsThis was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated metastatic colorectal cancer, presence of measurable lesions, age ≥20 years; Eastern Cooperative Oncology Group performance status of 0–2, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELOX (130 mg/m2 oxaliplatin on day 1 plus 1,000 mg/m2 capecitabine b.i.d. on days 1–14) every 3 weeks. The primary endpoint was confirmed objective response rate.ResultsThe study included 47 patients (male/female 30/17; median age 69 years; age range 38–81 years with 10 patients ≥75 years; PS 0/1/2, 40/5/2) enrolled between May 2010 and March 2011. Responses were assessed in 46 eligible patients. The objective response rate was 52.2 % (95 % confidence interval [CI] 37.0–67.1). The median progression-free survival and overall survival were 10.0 months (95 % CI 7.8–12.3) and 34.6 months (95 % CI 19.9–not estimable), respectively. Frequently encountered grade 3 and 4 adverse events in this study were aspartate aminotransferase elevation (23.4 %), alanine aminotransferase elevation (21.3 %), anorexia (12.8 %), neutropenia (10.6 %), fatigue (8.5 %) and anemia (6.4 %). Grade 3 or 4 peripheral neuropathy was not observed.ConclusionFirst-line treatment with XELOX plus bevacizumab showed a promising response rate and an acceptable tolerability profile in the clinical practice of Japanese metastatic colorectal cancer patients that included elderly patients.RegistryUMIN-CTR, ID number: UMIN000003915, URL:https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004706&language=E

Efficacy and safety of capecitabine plus oxaliplatin (XELOX) as the perioperative treatment of patients with potentially resectable liver-only metastases from colorectal cancer: A single arm, open-label, multicenter phase II trial (ML22298; NCT00997685).

777 Background: Surgical resection can improve survival of patients with resectable colorectal liver metastases (CLMs). Here, we investigatedthe efficacy and safety of XELOX as perioperative treatment for patients with potentially resectable CLM. Methods: Patients with potentially resectable liver-only metastases from CRC were enrolled. The primary endpoint of this study was progression-free survival (PFS); and the secondary endpoints included objective response rate (ORR), R0 resection rate, overall survival (OS) and safety profile of perioperative treatment of XELOX. Eligible patients were treated with XELOX (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1,000 mg/m2 b.i.d. for 14 days every 3 weeks). Tumor remission was assessed by CT after 6 weeks (2 cycles) of chemotherapy. Resectability of CLM was assessed by CT after 12 weeks (4 cycles) of chemotherapy. Adjuvant chemotherapy using XELOX was started within 8 weeks after hepatectomy. Results: Thirty patients (17 males and 13 females) were enrolled from 10 medical sites between January 2010 and October 2011, with median age of 57.5 years (range: 32-77). Median PFS was 336 days (95% CI: 173~385), and median OS was 912 days (95% CI: 516~1332). The ORR was 40% (12/30). The conversion rate from unresectable to resectable was 43.3% (13/30). Among these 11 patients who had received surgery (2 had withdrawn consent), 10 (90.9%) had received R0 resection. Subgroup analysis shows that patients who had received hepatectomy had longer median PFS [95% CI] (382 days [210~518] vs. 173 days [111~337], p = 0.0268) and median OS [95% CI] (1332 [721~NA] vs. 516 [295~1046], p = 0.005). There were 4 patients with post-operation complications of ascites and/or hydrothorax, and 3 patients had early chemotherapy termination due to drug-related AEs, including leukopenia, hepatotoxicity and diarrhea. Conclusions: Perioperative chemotherapy of XELOX is an option for patients with potentially resectable CLM due to the effect in prolonging PFS and OS, as well as the manageable toxicities and post-operation complications. Clinical trial information: NCT00997685.

The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: Final report of CCOG-0902 study.

e14552 Background: XELOX plus bevacizumab (BEV) is an established first line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty two patients (59%) were reintroduced oxaliplatin. After a median follow-up time of 24.2 months, median PFS was 13.4 months (95%CI: 11.7-15.1), median duration of disease control was 13.8 months (95%CI: 11.6-16.0) and median overall survival was 29.0 months (95%CI: 23.1-34.9). The response rate and disease control rate were 57.4% and 96.3% in the initial XELOX plus BEV therapy, 6.1% and 73.5% in Cape plus BEV maintenance therapy, and 0% and 72.4% in reintroduced XELOX plus BEV therapy. The incidence of neuropathy was 38% in initial therapy, 33% in maintenance therapy and 43% in reintroduced therapy. Conclusions: XELOX plus bevacizumab therapy with oxaliplatin stop-and-go strategy was feasible to maintain long disease control without increasing severe neurotoxicity in first-line treatment for mCRC. Clinical trial information: UMIN000006478.

Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer

The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m(2) on day 1, every 2weeks plus capecitabine 1000mg/m(2) (or capecitabine 750mg/m(2) if creatinine clearance was 30-50mL/min) twice daily on days 1-7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. Thirty-five patients were enrolled. Median age was 78years (range, 70-83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5-11.7) and 15.5 (95% CI: 9.6-21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1-2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.

The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: CCOG 0902 study.

564 Background: XELOX plus bevacizumab (BEV) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first-line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty one patients (59%) were reintroducted oxaliplatin. The response rates and disease control rates were 57% and 96% in the initial XELOX plus BEV, 6.1% and 73% in Cape plus BEV maintenance therapy. Median PFS in initial XELOX plus BEV was 11.0 months (95%CI: 7.8-14.1). One year survival rate was 86%. Conclusions: XELOX plus BEV was feasible as a first line treatment with mCRC. The most cases achieved disease control during Cape plus BEV maintenance therapy. Clinical trial information: UMIN000006478.

XELOX with bevacizumab in elderly patients age 75 or older with metastatic colorectal cancer: Results of a planned interim analysis for multicenter phase II ASCA study.

502 Background: Combination chemotherapy of capecitabine plus oxaliplatin (XELOX) with bevacizumab is commonly used as standard chemotherapy for metastatic colorectal cancer (mCRC). A previous meta-analysis showed that there was no difference between two age groups of <65 years and ≥65 years on overall survival (OS) after treatment with chemotherapy with bevacizumab. However, the safety and efficacy of XELOX with bevacizumab in elderly patients (pts) ≥75 years with mCRC remain unclear. Methods: This study was an open-label multicentre phase II study to evaluate the efficacy and safety of XELOX with bevacizumab in pts ≥75 years with metastatic CRC. The primary objective was to assess progression-free survival (PFS). The secondary endpoints were the safety, response rate (RR), time to treatment-failure (TTF) and OS. Results: 36 pts were enrolled. Pts characteristics were; median age 78 (range 75-86); male/female, 21/15; ECOG performance status 0/1, 30/6; colon/rectum 24/12, creatinine clearance (CCr) 60.2 ml/min (range 32.6-84.6). Median follow-up period was 220 days. RR was 55.6% and median TTF was 209 days. The median PFS and median OS are not reached. Grade 3 or 4 adverse events (AEs) were reported in 22 pts (62.8%). Common grade 3 or 4 AEs were hypertension (11.4%), leukopenia (20.0%), peripheral sensory neuropathy (14.3%), hand foot syndrome (8.6%), and fatigue (8.6%). Examining the relationship between renal function (CCr) and AEs, the incidence of Grade 3 or 4 AEs in the lower CCr group was significantly higher than that in the higher CCr group (61.6% vs. 47.8%; p=0.013); hematological toxicities (87.5% vs. 14.8%; p=0.0003) and non-hematological toxicities (61.5% vs. 11.1%; p=0.018). Conclusions: XELOX with bevacizumab is safely administered in elderly patients ≥75 years. Renal function (CCr) could be a good predictive marker for grade 3 or 4 AEs. Clinical trial information: UMIN000003500.

A prospective study of XELOX plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer (KSCC0902).

583 Background: XELOX plus bevacizumab (Bev) is one of the standard therapies for metastatic colorectal cancer (mCRC). However there was no clinical practice date in Japan. This study was designed to evaluate the efficacy and safety of XELOX plus Bev in the clinical practice in Japanese mCRC patients (pts) including the elderly. Methods: The study design was multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated mCRC; presence of measurable lesions; age 20 years; ECOG performance status (PS) 0–2; and adequate organ function. Pts received Bev 7.5 mg/kg d1 and XELOX (oxaliplatin 130 mg/m2 d1 plus capecitabine 1,000 mg/m2 bid d1-14) q3w. This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint was RECIST-confirmed objective response rate (ORR). A sample size of 41 was planned for a threshold ORR of 30% and expected value of 50%, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: Of the 47 pts (male/female, 29/18; median age, 66 years (range 38-81); PS 0/1/2, 40/5/2) enrolled from May 2010 to Mar 2011. One patient did not fulfill the eligibility criteria. 46 pts were assessed for response; CR 1 pts, PR 23 pts, SD 15 pts, PD 2 pts, and NE 5 pts. The confirmed ORR was 52.2% (90% CI, 39.2-65.0%). The response rate across all time points without confirmation was 67.4% (95% CI, 52.0-80.5%). Median PFS and OS have not yet been reached. The most common grade 3/4 adverse events were anorexia 12.8%, neutropenia 10.6%, fatigue 8.5%, hypertension 4.3%, thrombocytopenia 4.3%, hand-foot syndrome 2.1% and bleeding 2.1%. Grade 3/4 peripheral neuropathy did not occur. Conclusions: First-line treatment of XELOX + Bev showed a promising response rate and an acceptable tolerability profile in the clinical practice in Japanese mCRC pts including the elderly. Clinical trial information: UMIN000003915.

XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study

The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC. Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) on day 1, plus capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate. A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52% [95% confidence interval (CI) 37 to 68%], with 86% of patients achieving disease control. Median PFS and overall survival were 11.5 months (95% CI 10.0-12.9 months) and 19.3 months (95% CI 16.5-22.1 months), respectively. In all, 10 patients (23%) had grade 3/4 adverse events (AEs), the most common being diarrhea (9%), neutropenia (7%), peripheral neuropathy (7%), and stomatitis (7%). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population. The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.

P-0242 Xelox and Bevacizumab as First-Line Treatment in fit Elderly Patients with Metastatic Colorectal Cancer: The Boxe Study

ABSTRACT Introduction The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (MCRC). However, clinical trials have been conducted primarily in younger patients with only a small proportion of elderly patients. Moreover, an increased risk of arterial thromboembolic events has been observed in some trials in older patients. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in fit patients over 70 years of age with MCRC. Methods Treatment consisted of bevacizumab 7.5mg/Kg and oxaliplatin 130mg/m2 on day 1, plus capecitabine 1000mg/m2 twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients with a clinical response or stable disease could be maintained on bevacizumab monotherapy up to progressive disease. The primary study end-points were safety and response rate. Results A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52% [95% confidence interval (CI): 37% to 68%], with 86% of patients achieving disease control. Median PFS and overall survival were 11.5 months (95% CI: 10.0-12.9 months) and 19.3 months (95% CI: 16.5-22.1 months), respectively. Four patients (9%) underwent liver metastasectomy with curative intent. In all, 10 patients (23%) had grade 3/4 adverse events (AEs), the most common being peripheral neuropathy (7%), stomatitis (7%), diarrhoea (7%). No patients died because of treatment-related AEs. The low incidence of bevacizumab-associated AEs (hypertension, thromboembolic events and gastrointestinal perforation) was not consistent with that of previous reports in elderly patients. Conclusion XELOX plus bevacizumab is effective and has a manageable tolerability profile when administered to fit elderly patients with MCRC.

Efficacy and safety of XELOX and FOLFOX6 adjuvant chemotherapy following radical total gastrectomy

The purpose of this study was to compare the efficacy and safety of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) for advanced gastric cancer following total gastrectomy. We performed a retrospective study of 148 gastric cancer patients undergoing total gastrectomy combined with adjuvant chemotherapy from January, 2003 to June, 2009. The follow-up lasted until December, 2010. The Chi-square test and Kaplan-Meier methods were employed to compare the adverse events and prognosis. The total 1-, 3- and 5-year survival rates were 95, 80 and 32%, respectively, and there was no significant difference between the two groups (P=0.273). Similarly, the total incidence of side effects was similar, but each treatment was associated with unique disturbances. The number of patients developing hand-foot syndrome in the XELOX group was far higher compared to the FOLFOX6 group (P=0.000). By contrast, more patients in the FOLFOX6 group suffered from nausea (P=0.024), vomiting (P=0.029), alopecia (P=0.033) and peripheral phlebitis (P=0.004). The total completion rate of the XELOX group was higher compared to the FOLFOX6 group (P=0.015). No significant difference was found in the prognosis of patients receiving XELOX therapy or FOLFOX6 therapy following total gastrectomy. XELOX was, however, more tolerable for patients with total gastrectomy.

Preliminary results of an open label, uncontrolled, multicenter, phase II study evaluating the efficacy and safety of xelox plus cetuximab as first-line therapy in patients with metastatic colorectal cancer

15010 Background: At present, there are limited data available for the use of cetuximab in combination with Oxaliplatin and Capecitabine, in the first line treatment of metastatic colorectal cancer. This study aimed to determine the efficacy and safety of the combination Xelox and Cetuximab in this setting. Methods: Patients received intravenous Oxaliplatin 130mg/m2 (3h-day 1) plus oral Capecitabine 1,000mg/m2 twice daily (days 1–14) every 3 weeks (Xelox) and intravenous Cetuximab 400mg/m2 in week 1 followed by weekly doses of 250mg/m2. Treatment was continued until disease progression, intolerable toxicities or 8 cycles were reached. This study aimed to include 45 patients to obtain a 95%CI for the overall response rate (ORR-primary endpoint) with a maximum width of 15% assuming an ORR of 50–80%. Patients will be followed until death. Results: The ITT population of 49 patients was enrolled between September 2005 and January 2007. Mean age was 60 years (range:44–75 years) and 66% of patients were male. The ECOG performance status was zero in 56.2% of the patients and 72.9% of the patients had distant metastasis. 31 patients were evaluable for response in cycle 5. One patient (3.2%) achieved a CR, 17 (54.8%) had PR, 9 (29.0%) had SD, 2 (6.5%) had PD and 2 (6.5%) were non- evaluable. The ORR was 58% (95%CI:40.6%-75.4%) and the TTP was 12 months (95%CI:9.2–14.8 months). Survival and quality of life data will be available soon. 48 patients were evaluable for toxicity. 11.5% of the adverse events (AEs) were grade 3/4. 77.1% of the patients had skin rash but only 8.3% had grade 3/4. Other grade 3/4 toxicities included diarrhea (n=7;14.6%), changes in potassium (n=6;12.5%), fatigue (n=2;4.2%) and thrombosis (n=1;2.1%). 2.7% of the AEs led to dose reduction, 7.3% to dose delay and 0.3% to infusion rate reduction. 25 (52.1%) patients were discontinued: 8 (16.7%) due to AEs, 7 (14.6%) due to PD and 10 (20.8%) due to other reasons. Conclusions: Preliminary results show that an overall response was achieved in nearly 60% of the patients treated with the combination of Xelox and Cetuximab.In addition, this combination appears to be a well tolerated regimen. No significant financial relationships to disclose.

Phase II clinical trial of XELOX as first line treatment for patients with unresectable or metastatic gastric cancer

15062 Background: The survival of advanced gastric cancer remains poor, while no chemotherapy regimen was recognized standard. Oxaliplatin and Capecitabine (Xeloda) have demonstrated promising antitumor efficacy in advanced colorectal cancer. The present study was conducted to further evaluate the efficacy and safety of XELOX (Oxaliplatin and Xeloda) regimen in gastric cancer. Methods: Patients with unresectable or metastatic gastric cancer were enrolled into this study. They all receive the XELOX regimens (Oxaliplatin 130mg/ m2 intravenously in 2 hours on day 1 followed by oral capecitabine 1000mg/ m2 twice daily for 14 days every 3 weeks).We evaluated the response every 2 cycles. Results: The median age of the total enrolled 45 patients was 55 years (range, 22–82 years), including 32 male and 13 female. They received a median of 5 cycles (range, 2–8 cycles) of XELOX. 21 of 45 patients (46.7%) achieved an objective response, 1 patient (2.2%) had completed response. 17 patients (37.8%) experienced stable disease. Median time to tumor progression (TTP) and median overall survival were not available yet due to the further follow-up needed. Most toxicity events were mild to moderate in XELOX regimen, with grade 3/4 neutropenia of 8.9 %, thrombocytopenia of 6.7%, anemia of 11.1%, hand-foot syndrome of 6.7 % and diarrhea of 6.7 %. Grade 3 neuropathy was 4.4%. The patients with advanced gastric cancer had a good tolerance to this chemotherapy. Conclusions: XELOX is a highly effective first-line treatment for unrsectable and metastatic gastric cancer. The response rates in this trial seems to be similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX is tolerable well in the treatment of advanced gastric cancer. No significant financial relationships to disclose.

Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer

We evaluated efficacy and safety of XELOX in previously untreated patients with AGC. Patients received intravenous oxaliplatin 130 mg/m(2) over 2 h on day 1 plus oral capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks (XELOX). Treatment was continued until disease progression, intolerable toxicities or eight cycles reached. All tumour evaluations were reviewed and confirmed centrally. Design was according to Ensign's three-stage method. Fifty-four patients (37 men) were enrolled; median age 57 years (range 29-70). In total, 311 cycles of XELOX were delivered. Overall response rate was 63% (95% CI, 50-76%), with 3 complete and 31 partial responses. At 13 months' median follow-up, median progression-free and overall survival were 5.8 (95% CI, 4.4-7.2) and 11.9 months (95% CI, 8.8-15.1), respectively. The most common haematological adverse event was anaemia (70% of patients). Grade 3-4 neutropenia was observed in four patients, with neutropenic fever in only one patient. Most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrhoea (33%), and hand-foot syndrome (HFS) (39%). Grade 3-4 toxicities were rare. Treatment was delayed or the dose reduced in 30 and 15% of cycles, respectively. There was one treatment-related death associated with grade 4 neutropenic sepsis. XELOX was active and well tolerated as a first-line therapy for AGC.

Capecitabine plus oxaliplatin (XELOX) followed by capecitabine plus irinotecan (XELIRI) in a sequential schedule in first-line metastatic colorectal cancer (MCRC): a phase II multicenter study

13516 Background: In phase II trials, XELOX and XELIRI were highly active and well tolerated in first-line MCRC. The aim of this study is to explore the efficacy and safety of XELOX followed by XELIRI as first-line treatment in MCRC. Specifically, we wanted to evaluate the impact of sequential scheduling on the dose-limiting neurotoxicity associated with oxaliplatin accumulation. Methods: Eligible patients (pts) had histologically or cytologically confirmed MCRC, ECOG PS ≤ 2 and adequate bone marrow, renal and hepatic function. Prior chemotherapy for MCRC was not allowed. Pts received 4 cycles of XELOX (capecitabine 1000mg/m2 orally bid d1–14 + oxaliplatin 130mg/m2 i.v. d1, q3w) followed by 4 cycles of XELIRI (capecitabine 1000mg/m2 bid d1–14 + irinotecan 240mg/m2 i.v. d1, q3w). This sequential schedule was repeated until unacceptable toxicity or disease progression. Results: Of the 35 pts analized to date: M/F (69%/31%); median age 68 years (range 41–78); ECOG PS 0–1 (94%); surgery (77%) and adjuvant chemotherapy (31%). 240 cycles (median 6, range 1–16) have been administered. 35 pts received XELOX (123 cycles, median 4), and 21 pts received XELIRI (83 cycles, median 4) in the first sequential schedule. In the second sequential schedule 6 pts received XELOX (22 cycles, median 4) and 4 pts received XELIRI (12 cycles, median 3.5). Median relative dose intensity was 88% for XEL, 96% for OX and 92% for IRI. In 27 efficacy evaluable pts, the ORR was 48% (95% CI, 29–67%). Eight pts were not evaluable due to adverse events (n=6), ongoing treatment (n=1) and lost of follow up (n=1). Conclusions: This sequential schedule is active and well tolerated in first-line MCRC. The improvement/recovery of the oxaliplatin-related neurotoxicity during the XELIRI phase is also promising and allows the re-treatment with oxapliplatin in the next sequence without accumulating neurotoxicity. Final results will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.

Phase II multicenter sequential study of oxaliplatin (O) and capecitabine (C) followed by irinotecan (I) and capecitabine (C) in first line advanced colorectal cancer (CRC)

3544 Background: In phase II trials, XELOX and XELIRI were highly active and well tolerated in first-line MCRC. The aim of this study is to explore the efficacy and safety of XELOX followed by XELIRI as first-line treatment in MCRC. Specifically, we wanted to evaluate the impact of sequential scheduling on the dose-limiting neurotoxicity associated with oxaliplatin accumulation. Methods: Eligible pts had histologically or cytologically confirmed MCRC, ECOG PS ≤2 and adequate bone marrow, renal and hepatic function. Prior chemotherapy for MCRC was not allowed. Pts received 4 cycles of XELOX (capecitabine 1000mg/m2 orally bid d1–14 + oxaliplatin 130mg/m2 i.v. d1, q3w) followed by 4 cycles of XELIRI (capecitabine 1000mg/m2 bid d1–14 + irinotecan 240mg/m2 i.v. d1, q3w). This sequential schedule was repeated until unacceptable toxicity or disease progression. Results: Of the 29 pts enrolled to date: M/F (72%/28%); median age 69.6 years (range 41.2–78.8); ECOG PS 0–1 (93%). Previous treatment included surgery (83%), adjuvant chemotherapy (38%), and radiotherapy (14%). 146 cycles (median 4, range 1–16) have been administered. 28 pts received XELOX (88 cycles, median 4), and 11 pts received XELIRI (42 cycles, median 4) during the first sequential schedule. 3 pts received XELOX (9 cycles, median 4) and 2 pts received XELIRI (7 cycles, median 3.5) in the second sequential schedule. Median relative dose intensity was 94% for capecitabine, 100% for oxaliplatin and 97% for irinotecan. In 15 efficacy evaluable pts, the ORR was 47% (95% CI, 22–72%). 13 pts are not evaluable due to adverse events (n=4), ongoing treatment (n=8), or withdrawal of consent (n=1). There were no grade 4 events. Conclusions: Preliminary results show that this sequential schedule is active and well tolerated in first-line MCRC. The low rate of grade 3 neurotoxicity/paresthesia is also promising. No significant financial relationships to disclose.