Capecitabine (Xeloda®) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors

Dı́az-Rubio, Eduardo; Evans, T.R. Jeffry; Tabernero, Josep; Cassidy, James T.; Sastre, Javier; Eatock, Martin; Bisset, Donald; Regueiro, Pilar; Baselga, José

doi:10.1093/annonc/mdf065

Cited by 101 publications

(58 citation statements)

References 23 publications

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“…Cassidy et al (2004) reported the results of a phase II study of oxaliplatin plus capecitabine (XELOX) as a firstline therapy in patients with colorectal cancer (Díaz-Rubio et al, 2002). Oxaliplatin (130 mg m À2 ) was administered on day 1 and capecitabine (2000 mg m À2 day À1 ) for 14 days with a 1-week rest, every 3 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…In cases where sudden and severe thrombocytopaenia is observed, type II allergic reaction to oxaliplatin should be considered and definitive withdrawal is strongly suggested (Maindrault-Goebel et al, 2001). A phase I study of XELOX with 130 mg m À2 of oxaliplatin tri-weekly has also shown a relatively higher incidence of grade 3 thrombocytopaenia in 22% (Díaz-Rubio et al, 2002), but only 4% during phase II with weekly assessment of CBC (Cassidy et al, 2004). Thrombocytopaenia of SOX should be evaluated in the future phase II or III studies with a larger number of patients.…”

Section: Discussionmentioning

confidence: 99%

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Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer

Yamada¹,

Tahara

Miya

et al. 2008

Br J Cancer

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Two phase II studies of S-1 monotherapy have shown promising response rates (RR) of 35 -40% with good tolerability in patients with untreated metastatic colorectal cancer. To investigate the usefulness of S-1 plus oxaliplatin (SOX) as an alternative to infusional 5-fluorouracil/leucovorin plus oxaliplatin, the recommended dose (RD) of SOX was determined, and its safety and preliminary efficacy were evaluated in a phase I/II study. Oxaliplatin was administered at a dose of 100 mg m À2 (level 1) or 130 mg m À2 (level 2) on day 1, and S-1 (80 -120) was given twice daily for 2 weeks followed by a 1-week rest. This schedule was repeated every 3 weeks. Level 2 was determined to be the RD. For the 28 patients who received the RD, the median treatment course was 6.5 cycles (2 -14), RR of 50% (1 CR and 13 PR: 95% CI 31 -69%), with a median progression-free survival of 196 days. Survival rate (1 year) was 79%. Peripheral neuropathy was observed in all patients but with no functional disorders. Major grade 3 or 4 adverse reactions at the RD were neutropaenia (14%), thrombocytopaenia (28%), and diarrhoea (3%). SOX regimen is effective and easily manageable without central vein access. Potassium oxonate is an orotate phosphoribosyl transferase inhibitor that is distributed primarily to the gastrointestinal tract. This component of S-1 decreases incorporation of 5-fluorouridine triphosphate into RNA in the gastrointestinal mucosa and reduces the incidence of diarrhoea. F-b-alanine (FBAL) is the main metabolite of 5-FU. F-b-alanine and fluorocitrate are thought to cause the neurotoxic and cardiotoxic effects of 5-FU by inhibiting the tricarboxylic acid cycle (Okeda et al, 1990;Robben et al, 1993;Diasio 1998). The CDHP component of S-1 inhibits DPD, the rate-limiting enzyme in the catabolic pathway of 5-FU. Consequently, the plasma FBAL concentration after oral administration of S-1 is significantly lower than that after continuous infusion of 5-FU (Yamada et al, 2003). Therefore, S-1 may decrease the incidence of neurotoxicity and cardiotoxicity. The response rate of S-1 monotherapy has been found to be 35-40% for patients with metastatic colorectal cancer (Ohtsu et al, 2000;Shirao et al, 2004), with grade 3 or 4 neutropaenia observed in 5-13%, thrombocytopaenia in 0-8%, diarrhoea in 2-3%, and grade 1 hand-foot syndrome (HFS) in 5%.Oxaliplatin is a third-generation platinum compound with less toxicity and improved convenience. The regimen of infusional 5-FU and leucovorin (LV) with oxaliplatin is the standard for firstand second-line chemotherapy in patients with metastatic colorectal cancer (de Gramont et al, 2000;Rothenberg et al, 2003;Goldberg et al, 2004). However, infusional 5-FU with LV has the disadvantages of increased inconvenience, cost, and morbidity related to the use of a portable infusion pump and a central venous catheter. Therefore, oral fluoropyrimidine monotherapy has been commonly used in Japan.The primary objectives of this phase I/II study were to determine the maximum tolerated dose (MTD) of S-1 plus oxal...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer

Yamada¹,

Tahara

Miya

et al. 2008

Br J Cancer

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“…These include continuous capecitabine (7 days per week) with oxaliplatin given on days 1 and 29 (Glynne-Jones et al, 2006c), continuous capecitabine (5 days per week) with weekly doses of oxaliplatin (Machiels et al, 2005;Rutten et al, 2006) and discontinuous capecitabine (days 1 -14 and 22 -35) with oxaliplatin on days 1, 8, 22 and 29 (Roedel et al, 2003(Roedel et al, , 2007. The aim of the present multicentre phase II study was to evaluate the efficacy, tolerability and feasibility of preoperative capecitabine plus oxaliplatin in combination with radiotherapy as described by Roedel et al (2003Roedel et al ( , 2007, and to investigate the contribution of an additional single cycle of neoadjuvant capecitabine and oxaliplatin (XELOX regimen) (Díaz-Rubio et al, 2002;Cassidy et al, 2004) before the start of radiotherapy.…”

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confidence: 98%

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

et al. 2008

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This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m À2 bid on days 1 -14 and oxaliplatin 130 mg m À2 on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m À2 bid on days 22 -35 and 43 -56, and oxaliplatin 50 mg m À2 on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13 -36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

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“…However, G-CSFs were prescribed appropriately in intermediate-and low-risk patients at our institution. In previous study inappropriate prescribing of G-CSFs increase FN episodes with lung and colorectal cancer on chemotherapy regimens receiving G-CSFs, the probability of high, intermediate and low risk FN was 17%, 18% and 10%, respectively; and 96% of G-CSFs use were not based on guidelines [25][26][27][28][29][30][31][32][33][34][35][36]. In our study, the appropriateness of G-CSFs use was not associated with FN incidence in patients received chemotherapy regimens with high risk of FN potential.…”

Section: Discussionmentioning

confidence: 95%

Evaluation of the Use of Granulocyte Colony-Stimulating Factors (G-CSFs) for Neutropenia Primary Prophylaxis in Solid Tumors at a Tertiary Care Hospital, Retrospective Study

Af¹,

Alnatsheh²,

Aseeri³

et al. 2017

J Pharmacovigil

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Capecitabine (Xeloda®) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors

Cited by 101 publications

References 23 publications

Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer

Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

Evaluation of the Use of Granulocyte Colony-Stimulating Factors (G-CSFs) for Neutropenia Primary Prophylaxis in Solid Tumors at a Tertiary Care Hospital, Retrospective Study

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