OPTIMOX1: A Randomized Study of FOLFOX4 or FOLFOX7 With Oxaliplatin in a Stop-and-Go Fashion in Advanced Colorectal Cancer—A GERCOR Study

Tournigand, Christophe; Cervantes, Andrés; Figer, Arié; Lledo, Gérard; Flesch, M.; Buyse, Marc; Mineur, Laurent; Carola, Élisabeth; Etienne, Pierre-Luc; Rivera, Fernando; Chirivella, Isabel; Perez-Staub, N.; Louvet, Christophe; André, Thierry; Tabah-Fisch, Isabelle; Gramont, Aimery de

doi:10.1200/jco.2005.03.0106

Cited by 747 publications

(476 citation statements)

References 18 publications

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“…Although the incidence of grade 3 or 4 thrombocytopaenia seems to be higher with SOX compared with the reported result of FOLFOX4 (Diaz-Rubio et al, 1998;Shirao et al, 2004), it was well managed by adequate dose modification of oxaliplatin and S-1 in subsequent cycles (Goldberg et al, 2004). Since the severity of thrombocytopaenia is dependent on the dose of oxaliplatin, FOLFOX7 with oxaliplatin at a dose of 130 mg m À2 caused 9% of grade 3 thrombocytopaenia (Maindrault-Goebel et al, 2001;Tournigand et al, 2006). The median time to first dose reduction was five cycles (range: 2 -7) due to any reason in 16 of the 28 patients at the RD, and 4.5 cycles (range: 3 -5) due to grade 3 or 4 thrombocytopaenia in 6 of the 28 patients.…”

Section: Discussionmentioning

confidence: 92%

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: 92%

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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“…As toxicidades neurológicas, como parestesia e neuropatia periférica, são mais comuns quando em uso de oxaliplatina 21,[35][36][37][38] . Entretanto, na atual pesquisa, observou-se uma grande frequência de 39,40 deve-se considerar que todos os pacientes do presente estudo haviam sido submetidos a quimioterapia prévia, além de serem polimedicados.…”

Section: Discussionunclassified

“…O uso de antiinflamatórios não esteroidais (AINES) vem sendo indicado para a prevenção e tratamento da neuropatia periférica induzida pela oxaliplatina 38 . Além disso, a identificação do polimorfismo genéti-co 40 e variações/modificações dos tratamentos 16,37 são estratégias para a prevenção dessas reações.…”

Section: Discussionunclassified

Adverse drug reaction: a comparative analysis of protocols used for treatment of colorectal cancer

Melo¹,

Cardoso²,

Silva³

2017

Medicina (Ribeirão Preto)

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Modelo do estudo: Estudo de coorte. Objetivo: Analisar as reações adversas ocorridas em pacientes brasileiros com câncer colorretal submetidos ao tratamento quimioterápico com dois protocolos distintos, visando identificar os tipos e a severidade das alterações mais frequentes. Método: Foram avaliados 63 pacientes, que iniciaram tratamento entre junho de 2014 a maio de 2015 em uma instituição do Rio de Janeiro, subdivididos em dois grupos: protocolo mFOLFOX6 (esquema contendo oxaliplatina 85mg/m2, ácido folínico 400mg/m2 e 5-fluorouracil em infusão em bolus 400mg/m2 e contínua 2.400mg/ m2, n= 40) e protocolo FOLFIRI (esquema contendo irinotecano 180mg/m2, ácido folínico 400mg/m2 e 5-fluorouracil em infusão em bolus 400mg/m2 e contínua 2.400mg/m2, n= 23). Foram coletados do prontuário dados relacionados ao perfil demográfico e clínico dos pacientes, além de informações do tratamento realizado e das toxicidades manifestadas. As toxicidades foram classificadas quanto à gravidade (graus 1, 2, 3 e 4) e causalidade (definida, provável, possível e duvidosa). Resultados: Foi observada alta frequência de toxicidades em ambos os grupos, atingindo 92,5% dos pacientes com protocolo mFOLFOX6 e 95,6% com protocolo FOLFIRI. As toxicidades gastrointestinais e neurológicas foram as mais frequentes, independente do grupo. Ao comparar a ocorrência das reações intergrupos, houve diferença apenas para as toxicidades gastrointestinais (p=0,035). Em 17,5% dos pacientes do grupo mFOLFOX6 (n= 7) e em 8,7% do grupo FOLFIRI (n= 2) se observou toxicidades dos tipos 3 e 4, sendo estas classificadas como provável reação adversa aos medicamentos. Conclusão: As toxicidades foram mais variadas e frequentes no grupo mFOLFOX6 em comparação ao grupo FOLFIRI. Entretanto, não se observou diferença na severidade e na causalidade das reações ocorridas em ambos os grupos.

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“…Наибольшее время без ХТ было отмечено в группе пациентов с хорошим соматическим статусом (ECOG -0-1), низким уровнем лактатдегидрогеназы (ЛДГ) и щелочной фосфатазы (≤ 3 верхним границам нормы), небольшой распространенностью опухолевого процесса (≤ 1 органа, пораженного метастазами) [2]. Отметим, что в качестве факторов неблагоприят-ного прогноза при совокупном анализе данных 3 ис-следований -OPTIMOX1 (сравнение схемы FOLFOX4 до прогрессирования и интермитирующей ХТ по схеме FOLFOX7) [3], OPTIMOX2 и C97-3 (схемы FOLFIRI в 1-й линии и FOLFOX6 во 2-й против обратной по-следовательности) -были выделены следующие при-знаки неблагоприятного прогноза: низкий соматичес-кий статус (ECOG 2), высокий уровень ЛДГ (> 1 верхней границы нормы), поражение метастазами > 1 органа [4]. Также при анализе исследований OPTIMOX1 и OPTI-MOX2 было выявлено, что пациенты с нормальным уровнем РЭА выигрывали от «ХТ-каникул» по сравне-нию с больными, которым продолжали ХТ до прогрес-сирования [5].…”

Section: рис 1 выживаемость без прогрессированияunclassified

Factors associated with the efficiency of maintenance therapy in patients with metastatic colorectal cancer

Федянин¹,

Трякин²,

Полянская³

et al. 2016

Onkol. koloproktol.

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OPTIMOX1: A Randomized Study of FOLFOX4 or FOLFOX7 With Oxaliplatin in a Stop-and-Go Fashion in Advanced Colorectal Cancer—A GERCOR Study

Abstract: Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.

Cited by 747 publications

References 18 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

Adverse drug reaction: a comparative analysis of protocols used for treatment of colorectal cancer

Factors associated with the efficiency of maintenance therapy in patients with metastatic colorectal cancer

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