Modified Folinic Acid-Fluorouracil-Oxaliplatin (FOLFOX) Followed by Capecitabine as First-line Chemotherapy for Elderly or Frail Patients With Metastatic or Recurrent Gastric Cancer
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 47
- 试验地点
- 2
- 主要终点
- progression-free survival
研究概览
简要总结
Elderly patients are generally underrepresented in the study populations of combination chemotherapy trials. In gastric cancer patients, oxaliplatin has shown a more favorable toxicity profile than cisplatin. A combination chemotherapy of 5-fluorouracil (5-FU) with oxaliplatin, mainly FOLFOX regimens, has been investigated in numerous phase II studies, using different doses and schedules, and has shown considerable antitumor activity. Insofar as toxicity is concerned, significant toxicities, including myelo-suppression and peripheral neuropathy, are a major issue for elderly patients. A modified FOLFOX regimen by omitting the administration of bolus 5-fluorouracil have shown a good profile of activity and tolerability in the elder population. This study evaluates the efficacy and safety of a modified FOLFOX (m FOLFOX) regimen for up to 8 cycles followed by capecitabine maintenance in elderly patients with metastatic gastric cancer and presenting associated disease(s)
详细描述
Although the number of deaths from gastric cancer has declined during the past, a large proportion of elderly patients are primarily affected by the disease. The definition of an elderly patient varies according to social and economic situations. However, in most developed and developing countries, 65 or 70 years of age is a commonly used limit because of the decreased role of the subject in the community and society.
Elderly cancer patients often suffer multiple comorbidities, take many medications, and have age-associated physiological problems, such as impaired organ function and functional changes, that make the selection of optimal treatment difficult. This aspect is also hampered by the underrepresentation of older patients in cancer clinical trials. Elderly patients who fulfill the inclusion criteria of clinical trials could experience the same advantages and toxicities from chemotherapy as younger patients. In contrast to physicians' perceptions, older patients do not recognize their age as an important issue for refusing trials [4]. Furthermore, performance status is not helpful to estimate the general condition of elderly patients, and other factors regarding their functional, social, and mental status should be considered [5].
Although the majority of gastric cancer patients are elderly, patients older than 65-70 years have been often excluded from, or underrepresented in, the study populations of combination chemotherapy trials.
There is, moreover, a lack of prospective studies directly comparing the outcomes and the tolerability of chemotherapy in young and elderly patients, although some data are available in gastric cancer from a retrospective analysis . Trumper et al. evaluated retrospectively 1,080 patients who were enrolled into three randomized controlled trias assessing 5-FU-based combination chemotherapy. They found that elderly patients obtained similar benefits from palliative chemotherapy in terms of symptomatic response, tumor regression, and survival, without increased toxicities.
In gastric cancer patients, oxaliplatin has shown a more favorable toxicity profile than cisplatin . A combination chemotherapy of 5-FU with oxaliplatin, mainly FOLFOX regimens, has been investigated in numerous phase II studies, using different doses and schedules, and has shown considerable antitumor activity. Insofar as toxicity is concerned, significant toxicities, including myelo-suppression and peripheral neuropathy, are a major issue for elderly patients. When compared to standard FOLFOX schedules, both weekly and biweekly reduced-dose combinations of oxaliplatin/5- FU without 5-FU bolus showed a more favorable toxicity profile with lower rates of peripheral neuropathy and myelosuppression.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 65 Years 至 99 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elderly patients (aged ≥65 years)
- •Histologically or cytologically confirmed gastric adenocarcinoma, including gastric or gastroesophageal-junction adenocarcinoma (GEJ)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (0-1 for patients aged ≥70 years, or with important comorbidity);
- •Measurable disease (revised RECIST) version 1.
- •based on computed tomography
- •Adequate bone marrow, hepatic, and renal function, as evidenced by:
- •At least 4 weeks and recovery from effects of prior major surgery or radiation therapy
- •Ability to swallow an oral solid-dosage form of medication, including when a feeding tube is present
- •A negative serum pregnancy test within 7 days prior to accrual in women of childbearing potential (that is, all women except those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization)
- •Agreement to use an effective form of contraception
- •Ability to comprehend and to comply with the requirements of the study
- •Estimated life expectancy ≥3 months
- •Adequate information and subsequent written informed consent
排除标准
- •Previous chemotherapy for metastatic/recurrent disease, except adjuvant chemotherapy completed at least 12 months before enrollment,
- •Previous treatment with oxaliplatin
- •Squamous cell gastric carcinoma
- •Bone-only metastatic disease significant gastrointestinal bleeding ,
- •Peripheral-neuropathy > grade 2, History or presence of brain metastasis or leptomeningeal disease
- •Operable gastric or GEJ cancer
- •Herceptin (HER) 2 positive disease if the subject has not previously been treated with an anti -Herceptin (HER) 2 agent
- •Uncontrolled diarrhea, defined as more than 3 loose bowel movements above the subject's usual number of bowel movements on at least 3 days within the 14 days prior to study entry
- •Nausea or vomiting for at least 3 consecutive days within the 14 days prior to study entry despite the administration of standard antiemetic therapy
- •Known malabsorptive disorder
- •Second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for 5 or more years)
- •Human immunodeficiency virus infection based on history of positive serology
- •Significant medical disease other than gastric cancer, including but not limited to uncontrolled diabetes mellitus, active angina or heart failure, uncontrolled hypertension, or an active psychiatric condition that would prevent consistent and compliant participation in the study
- •Presence of neuropathy > Grade 1
- •Prior radiation therapy to more than 25% of the bone marrow
- •Need for other anticancer treatment (such as chemotherapy, radiation therapy, or biologic therapy with an approved or investigational agent) while receiving protocol therapy
- •History of severe or unexpected reaction to fluoropyrimidine therapy
- •History of hypersensitivity to fluoropyrimidine agents or any of their ingredients.
- •Known dihydropyrimidine dehydrogenase deficiency
- •Pregnancy or lactation
研究组 & 干预措施
modified folfox
Oxaliplatin 85 mg/m2 in 2 hours intravenous infusion, + S-leucovorin 200 mg/m2, + 5-FU 2,400 mg/m2 as a 46 hours continuous infusion. The cycles are repeated every 2 weeks for a total of 8 cycle, if tumor response is stable disease, partial or complete response, then maintenance with Capecitabine 1,000 mg twice a day will be administered until disease progression, unacceptable toxicity or treatment refusal by the patient.
干预措施: FOLFOX (Drug)
modified folfox
Oxaliplatin 85 mg/m2 in 2 hours intravenous infusion, + S-leucovorin 200 mg/m2, + 5-FU 2,400 mg/m2 as a 46 hours continuous infusion. The cycles are repeated every 2 weeks for a total of 8 cycle, if tumor response is stable disease, partial or complete response, then maintenance with Capecitabine 1,000 mg twice a day will be administered until disease progression, unacceptable toxicity or treatment refusal by the patient.
干预措施: Capecitabine (Drug)
结局指标
主要结局
progression-free survival
时间窗: 6 months
progression-free survival
次要结局
- time to treatment failure(12 months)
- overall survival(12 months)
- number of patients with adverse events(12 months)
- PFS on capecitabine maintenance(6 months)
研究者
Vincenzo Catalano
Dr.
International Group of Endovascular Oncology