Anti-EGFR (cetuximab) combined with irinotecan for treatment of elderly patients with metastatic colorectal cancer (mCRC)

Purpose

This study was conducted to test the efficacy and toxicity of cetuximab and irinotecan as a biweekly regimen in treatment of elderly patients with metastatic colorectal cancer (mCRC).

Patients and methods

Forty-nine elderly patients (≥65?years) with mCRC who progressed after at least one previous line of treatment were enrolled into this study from May 2008 to January 2011. All recruited patients received cetuximab 500?mg/m² and irinotecan 180?mg/m² every 2?weeks.

Results

Thirty-seven patients (76?%) were men, and 76?% of patients had colonic cancer in origin. Median age was 69?years. Median overall survival time was 7?months, and median progression-free survival was 4?months. Grade 3–4 skin rash occurred in 20?% of patients, grade 3–4 diarrhea in 18?% of patients, and neutropenia in 28?% of patients.

Conclusion

Cetuximab combined with irinotecan when administered biweekly is safe and effective for treatment of pretreated elderly patients with mCRC.     

Oxaliplatin-based chemotherapy for the treatment of a metastatic carcinoid tumor

Carcinoid tumors are rare and often resistant to chemotherapy agents. Although a slow-growing tumor, patients can have significant morbidity associated with carcinoid syndrome and patients will often die as a result of tumor progression. We report the first case of a patient with a metastatic carcinoid tumor to respond to an oxaliplatin-based regimen. Further studies are needed to validate this observation.     

复方斑蝥胶囊联合化学治疗对转移性结直肠癌的疗效观察

目的 观察复方斑蝥胶囊联合奥沙利铂(L-OHP)、5-氟尿嘧啶/亚叶酸钙(5-FU/CF)组成的FOLFOX4方案治疗转移性结直肠癌的临床疗效及不良反应.方法 收集2006年4月至2008年10月收治的无手术指征的转移性结直肠癌患者107例,随机分为复方斑蝥胶囊联合FOLFOX4方案组(联合治疗组)54例和FOLFOX4方案组53例.联合治疗组给予L-OHP 85mg/m2,第1天静脉滴注2 h,同时或之后予CF 200 mg/m2,静脉滴注2 h,续5-FU 400 mg/m2静脉推注,600 mg/m2持续静脉滴注22 h,次目重复,CF与5-FU每2周重复一次,同时予以复方斑蝥胶囊口服750 mg,每天2次.FOLFOX4方案组患者单纯接受FOLFOX4方案化学治疗.结果 联合治疗组和FOLFOX4方案组有效率分别为44.4%和37.7%,两组间差异无统计学意义(P=0.481).联合治疗组的中位无进展时间(TTP)为11.6个月,FOLFOX4方案组为7.9个月,两组间差异有统计学意义(P=0.020).生活质量评价,联合治疗组的改善率为57.4%,FOLFOX4方案组为32.1%,两组间差异有统计学意义(P=0.008).两组不良反应主要表现为消化道反应、神经系统毒性、脱发和骨髓抑制.联合治疗组Ⅲ/Ⅳ度粒细胞减少发生率为37.0%,FOLFOX4方案组为58.5%,两组间差异有统计学意义(P=0.043).结论 复方斑蝥胶囊联合FOLFOX4方案一线治疗转移性结直肠癌能协同增效,能提高患者TTP及改善患者生活质量,降低粒细胞减少发生.     

Chemotherapy associated hepatotoxicity in the treatment of advanced colorectal cancer (CRC)

Modern combination chemotherapies, mainly including oxaliplatin or irinotecan, have demonstrated a significant increase in response rates. This led to the concept of down-sizing irresectable liver metastases from colorectal cancer, thereby achieving secondary resectability and possibly cure. However, these benefits of preoperative chemotherapy must be weighed against potential side effects to the surrounding normal liver tissue. In particular, in patients with pre-existing liver disease combination therapy can cause liver damage which may exceed mere steatosis of hepatocytes and lead to inflammation, cholestasis and bleeding. In correspondence to the "non-alcoholic steatohepatitis" (NASH) the term "chemotherapy associated steatohepatitis" (CASH) has been proposed in the literature. Platinum derivatives, in particular, can lead to damage of the hepatic microcirculation and the so-called sinusoidal obstruction syndrome (SOS). Few reports mention an increase in perioperative morbidity after combination chemotherapy. However, there are no comprehensive data on the individual risk of a patient for postoperative complications. If elevated liver enzymes are detected before chemotherapy and cannot readily be explained through liver involvement by the tumor, then close monitoring of enzymes should be performed and a biopsy may be considered in unclear cases. We recommend that the histological changes observed in the liver be quantified and classified by a unifying scoring system and propose, in correspondence to the hepatitis activity scores, a modified scoring system.     

Role of chemotherapy and novel biological agents in the treatment of elderly patients with colorectal cancer

Patients older than 65 years are the fastest growing segment of the cancer population. It is estimated that within 20 years over 75% of cases and 85% of deaths from colorectal cancer （CRC） will be in this setting. Concerns about cancer treatment in the elderly relate to comorbidities, which increase proportionally with age, physiological changes associated with aging which may influence drug metabolism and toxicity, and diminishing life expectancy, which particularly impacts decisions surrounding the benefits of adjuvant therapies. Over the last 10 years, significant improvements in the treatment of advanced CRC with combination therapy have been made. The randomized trials which have defined these improvements did not exclude elderly patients. However, the median age of patients in these trials has generally been approximately 60 years. Thus, it appears that some degree of selection is involved with younger and presumably fitter patients being the subjects in most of the pivotal trials. The availability of new molecularly targeted agents and newly improved existing agents has expanded the range of treatment options available. This variety gives greater flexibility in dealing with different subsets of patients, such as the elderly. However, some fit elderly patients seem to tolerate combination therapy reasonably well, while studies on unfit elderly subjects are needed.     

Current place of high-dose irinotecan chemotherapy in patients with metastatic colorectal cancer

Introduction  Irinotecan has an important place in the treatment of metastatic colorectal cancer. It was initially administered as monotherapy, but is now generally used in combination with 5-fluorouracil or targeted therapies (cetuximab or bevacizumab), with various doses. Methods  We here review the main studies assessing irinotecan doses escalation, and discuss the potent advantages of this escalation. Results  Several studies have demonstrated a dose–intensity relationship for irinotecan, and high doses (up to 600 mg/m² as monotherapy, 260 mg/m² in combination therapy) have been used with satisfactory safety and higher objective response rates. It is possible that, in practice, some patients receive insufficient doses of irinotecan. Dose escalation could be considered in carefully selected patients: young patients with a good performance status and normal liver function. This approach could be useful in patients with liver metastases, which may become resectable in the case of a major tumour response. It is wise to perform UGT1A1 genotyping prior to dose escalation to detect patients at high risk of toxicity (genotype 7/7). The role of another laboratory parameter, which needs to be evaluated is the KRAS status of the tumour. A KRAS mutation confers resistance to cetuximab, which reduces treatment options, especially in first-line. However, in the CRYSTAL trial comparing FOLFIRI to FOLFIRI-cetuximab as first-line therapy, the presence of a KRAS mutation did not appear to influence the efficacy of FOLFIRI. The value of irinotecan dose escalation needs to be determined in this setting. Conclusion  Irinotecan dose escalation is potentially of interest in highly selected patients, but this concept is only based on phase I or II trials and must be validated by a randomized trial. Its value regarding other regimens such as FOLFIRINOX or combinations with targeted therapies also needs to be determined.     

FOLFOX4 in the treatment of metastatic colorectal cancer in elderly patients: A prospective study

Elderly patients constitute a subpopulation with special characteristics that differ from those of the general population and have been under-represented in clinical trials. We, prospectively, analyzed the toxicity and efficacy of the original FOLFOX4-regimen in the treatment of elderly patients affected by metastatic (m) colorectal cancer (CRC). Thirty-six consecutive patients aged 67-82 years (median age 72 years), 22 males and 14 females, with mCRC and measurable disease, were enrolled in the study. The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. A total of 36 patients, aged 67-82 years were included. Twenty-two and 14 patients were male and female, respectively. The median age was 72 years (range 67-82). The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The overall response rate (ORR) was 44.4% and similar to original study. Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 16 months. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. Tolerability, however, was manageable and no toxic death occurred. FOLFOX4-regimen maintains its efficacy, and safety ratio in elderly patients with mCRC and good performance status. It would be considered the treatment of choice in the treatment of this particular setting of patients.     

Capecitabine-based chemotherapy for metastatic colorectal cancer

Purpose  

Metastatic colorectal cancer (MCRC) remains a significant public health concern. The objectives of present study are to investigate the efficacy and safety profile of capecitabine-based chemotherapy in the treatment of MCRC.     

Irinotecan in the treatment of elderly patients with advanced colorectal cancer

Irinotecan is an active drug in the first and subsequent lines of chemotherapy for patients with advanced colorectal cancer. Frequently, the elderly patients are excluded from receiving irinotecan alone or in combination, and on many occasions these patients receive an initial reduced dose of this drug. This revision has been focused in the role of irinotecan in elderly patients.Material and methodsData from pharmacokinetic studies, comparative analysis of prospective trials according to age and prospective studies with irinotecan alone or irinotecan-combinations in the elderly have been revised and put into context.ResultsEither pharmacokinetic and clinical data suggest that fit elderly patients may tolerate irinotecan as well as the younger population. Response rate and survival achieved in elderly patients with irinotecan combinations seem to be equivalent to that obtained in younger patients.ConclusionElderly patients with advanced colorectal cancer should be carefully evaluated in order to be classified as fit or not fit through a comprehensive geriatric assessment. For the group of fit elderly patients, irinotecan may be used as in the younger population.     

Economic evaluation of colorectal cancer (CRC) screening

Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed once common economic evaluation standards are established in order to alleviate the methodological heterogeneity prevailing in study results.     

Bimonthly 5-fluorouracil in elderly patients with metastatic colorectal cancer. Study of 50 patients

PURPOSE: Recent advances in the management of colorectal cancer have improved the quality of life and the survival of patients treated with chemotherapy. In order to define the contribution of chemotherapy in elderly patients, we studied the tolerance and the efficacy of first-line chemotherapy in patients with metastatic colorectal cancer. METHODS: Patients aged over 75 years received, as outpatient therapy, a bimonthly 48 h leucovorin and fluorouracil regimen. Evaluation was assessed every six cycles (i.e., three months). RESULTS: Fifty patients were studied: 28 males and 22 females, aged between 75 to 87 years, 37 with colon cancer and 13 with rectal cancer. Among 45 patients capable of being evaluated, the response rate was 44%, with six complete responses (13%) and 14 partial responses (31%). Eighteen patients had stable disease (40%) and seven patients progressive disease (16%). Median progression-free survival was 8.8 months and median survival 16.4 months. Grade 3 to 4 toxicity occurred in 20% of the patients. Performance status improved in 56% of the patients. CONCLUSION: The bimonthly regimen is well tolerated in elderly patients and appears to prolong survival as well in younger patients.     

Carcinoembryonic antigen in monitoring of response to systemic chemotherapy in patients with metastatic colorectal cancer

The response to chemotherapy of solid tumors is generally assessed by measuring tumors visualized by imaging. However, the response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging, such as diffuse peritoneal dissemination. We evaluated the correlation between the change on imaging and change in CEA levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. Between July 1993 and August 1999 we retrospectively examined 136 patients with metastatic colorectal carcinoma, all of whom had measurable lesions. Forty patients received oral tegafur-uracil (300 mg/m2/day) plus folinic acid (60 mg/day) for 4 weeks, repeated every 5 weeks, as the firstline treatment. Another 96 patients received either a weekly intravenous bolus injection of 5-fluorouracil (400 mg/m2) plus folinic acid (20 mg/m2), or an intravenous bolus injection of 5-fluorouracil (425 mg/m2) plus folinic acid (20 mg/m2) for 5 consecutive days every month. Responders, based on CEA assessment, were defined as those with a greater than 50% drop in CEA level for more than 4 weeks. The pretreatment CEA levels were elevated beyond the normal cutoff value in 110 (81%) patients. A response rate of 18.4% (95% CI, 11.9-24.9%), including 8 complete remissions and 17 partial remissions, was achieved according to imaging studies. The response rate assessed by CEA was 25% (34/136). Sixteen responders (47%) based on CEA had no remission on imaging. The sensitivity of change in CEA levels in the prediction of true responders and progressive diseases on imaging were 72% and 81%, respectively. In terms of the positive predictive value, change in CEA levels in the prediction of true responders and progressive disease on imaging were 53% and 85%, respectively. Patients with remarkable falls on CEA levels survived significantly longer than nonresponders (P < 0.001, log-rank test). At follow-up of 48 months the median survival for responders and nonresponders assessed by CEA was 28 months and 13 months, respectively. These data suggest that measurement of CEA levels might be helpful in monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice. Furthermore, measurement of CEA levels may be helpful in determining the prognosis of patients with metastatic colorectal cancer receiving chemotherapy.     

The role of uracil-tegafur (UFT) in elderly patients with colorectal cancer

5-Fluorouracil (5-FU) administered in several schedules since its introduction in 1957 continues to be an integral part of standard first-line therapy for colorectal cancer. Continuous intravenous (i.v.) infusion appears to yield improved response rate and overall survival, with fewer adverse effects compared with i.v. bolus dosing. However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications (i.e. increased risk of infection and clotting and/or dislodgement of the catheter, increased risk of venous thrombosis). Colorectal carcinoma is the second cause of death for tumour after lung cancer. About 70% of cases occur over 65 years and 50% or more affects people over 70. In clinical research age was a common exclusion criteria and little information is available about the efficacy, safety and toxicity of chemotherapy in elderly patients because few studies focused on the treatment of cancer in that part of population. The goal of this article is to review the literature concerning the treatment of elderly patients with UFT, an orally administered dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine.     

老年人结直肠癌的围手术期治疗

目的 探讨老年性结直肠癌的临床特点和围手术期治疗.方法 回顾分析104例老年结、直肠癌的临床资料,比较围手术期治疗.结果 99例(95.2%)患者痊愈或好转出院.围手术期发生肺部感染13例(12.5%),其中6例(5.8%)发生呼吸衰竭;下肢深静脉血栓3例(2.9%);切口感染6例(5.8%);切口裂开2例(1.9%);肠瘘1例(1.0%);胃瘫1例(1.0%).因术后多器官功能衰竭死亡5例(4.8%).结论 老年人不是外科治疗老年结直肠癌的手术禁忌证,重视围手术期正确及时的处理可以减少术后并发症,改善患者生活质量.