Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

Scheithauer, Werner; Kornek, Gabriela; Raderer, Markus; Schüll, Birgit; Schmid, Katharina; Kovats, E.; Schneeweiß, Bruno; Lang, Fritz; Lenauer, Alfred; Depisch, D.

doi:10.1200/jco.2003.09.016

Cited by 162 publications

(84 citation statements)

References 21 publications

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“…This was achieved by administering the fluoropyrimidine at higher dose for 7 days during each 14-day cycle. Additionally, this regimen was associated with increased response rates and time to progression (Scheithauer et al, 2003). It is conceivable that, by adopting a similar schedule in combination with 2-weekly irinotecan, the efficacy of our regimen could be improved.…”

Section: Discussionmentioning

confidence: 98%

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

et al. 2006

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We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m À2 on day 1; capecitabine 850 mg m À2 12-hourly on days 1 -9. Level 2: as level 1 but capecitabine 1000 mg m À2 . Level 3: as level 2 but irinotecan 180 mg m À2 . Level 4: as level 3 but capecitabine 1250 mg m À2 . In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3 -4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16 -52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.

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Section: Discussionmentioning

confidence: 98%

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

et al. 2006

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“…Patients randomised to the raltitrexed-arm received a dose of 3 mg m À2 given on day 1 every 3 weeks. The last trial was also a randomised multicentre phase II study of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer (Scheithauer et al, 2003). Half of the patients received oxaliplatin 130 mg m À2 on day 1 plus capecitabine 2000 mg m day on days 1 -14 every 3 weeks, in the other treatment arm patients received oxaliplatin 85 mg m À2 on days 1 and 14 combined with capecitabine 3500 mg m À2 day on days 1 -7 and 14 -21 every 4 weeks.…”

Section: Chemotherapymentioning

confidence: 99%

Side effects during chemotherapy predict tumour response in advanced colorectal cancer

et al. 2005

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To investigate whether a relationship between chemotherapy-associated adverse events and treatment efficacy exists, we have analysed the toxicity, objective response and survival data of 303 patients with advanced colorectal cancer. Patients were divided into two groups: the first with beneficial effect (I, n ¼ 245), and the second with progressive disease (II, n ¼ 58). Differences in terms of incidence rates, type and severity of adverse events were analysed with univariate and multivariate models. The median number of side effects in group I was 6 vs 4 in group II (OR ¼ 1.342; P ¼ 0.0001). An inverse correlation between disease control and treatment tolerance was confirmed when side effects were analysed according to severity and type of treatment-associated toxicities (haematological: P ¼ 0.0005 vs nonhaematological P ¼ 0.0001). When median survival was analysed according to the number of adverse events, it was 10 (95% CI, 3 -7), 16 (14 -18), and 18 (16 -20) months in case of 0 -1, 2 -5, and X6 adverse events, respectively (P ¼ 0.01). In conclusion, the results of this analysis suggest that occurrence of side effects during chemotherapy in advanced colorectal cancer is an independent and reliable prognostic indicator for response and survival.

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“…Standard combination chemotherapy regimens comprising 5-fluorouracil (5-FU) plus leucovorin [LV] in combination with irinotecan, typically FOLFIRI or oxaliplatin (FOLFOX) have been reported to facilitate the resection of 9-40 % of initially unresectable metastases, and a median survival of 15 to 20 months [7][8][9]. Although, intensified chemotherapy such as FOLFOXIRI (i.e., oxaliplatin, 5-FU/LV and irinotecan) has been shown to have high response and conversion rates (19 %); however, it has not been generally recommended thus far due to its considerable toxicity [10].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Tumor Response and Resection Rates in Unresectable Colorectal Liver Metastases Following Neoadjuvant Chemotherapy with Cetuximab

Somashekhar

Ashwin

Zaveri

et al. 2015

Indian J Surg Oncol

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To investigate efficacy and safety of cetuximab combined with neo adjuvant chemotherapy regimen in patients with unresectable colorectal liver. This was a prospective trial with rate of Ro liver metastases resection as primary end point. Between January 2010 and December 2014, 46 patients with unresectable liver metastases from colon or rectum were enrolled. Patients received Cetuximab along with neoadjuvant chemotherapy where 34 (74 %) and 12 (26 %) patients received FOLFOX and FOLFIRI, respectively. They were assessed for response after 2-3 cycles by CT scan. Patients with resectable disease were offered liver surgery within 3-6 weeks of the last treatment cycle. The primary end point was resection rate of liver metastases, which was evaluated in all patients. Secondary end points were response rate according to Response evaluation criteria in solid tumors (RECIST) criteria, perioperative morbidity and mortality. An objective response was observed in 28 (60.9 %) patients. Seven (15.2 %) patients were reported radiologically to have a complete response (CR); 21 (45.7 %) patients had radiological partial response (PR). An additional 12 patients (26.1 %) demonstrated stable disease (SD) and only six patients (13.0 %) had disease progression (PD). Microscopically complete resections (R0 resection) was performed in all 28 patients (60.9 %). The most frequent toxicities were skin rash and diarrhoea. There was no operative mortality. Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. Complete resection of previously unresectable colorectal liver metastases can be performed with minimal morbidity and mortality. This therapeutic strategy involves a multimodal approach.

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Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

Abstract: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

Cited by 162 publications

References 21 publications

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

Side effects during chemotherapy predict tumour response in advanced colorectal cancer

Assessment of Tumor Response and Resection Rates in Unresectable Colorectal Liver Metastases Following Neoadjuvant Chemotherapy with Cetuximab

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