Chemotherapy for colorectal cancer in the elderly.
Colorectal cancer (CRC) is a disease that predisposes the elderly, with approximately 70% of patients older than 65 years and 40% older than 75 years, according to SEER data. In recent years, overall survival of CRC patients has improved significantly due to improvements in treatment, but survival improvements in older patients have not been significant.
Overview of the current state of treatment.
Poor survival outcomes in older patients are associated with many factors, such as poorer economic conditions, limited health resources, and more comorbidities. Inadequate treatment is probably the most important factor contributing to poor survival in older adults with CRC. Reasons for inadequate treatment include inadequate interventional diagnostic evaluation, incomplete surgery, and inadequate intensity of chemotherapy.
Evaluation of older patients.
Assessing whether the benefit of treatment can outweigh the risk of complications or death is the main issue to be weighed in the treatment of elderly CRC patients. Older patients imply an increase in age-related health problems (e.g., comorbidities, disability, physical and cognitive decline, etc.) and an increased incidence of cancer, and the proper selection of patients for effective and safe treatment becomes critical. Aging states should undergo a geriatric assessment (CGA), an in-depth assessment of the older patient’s comorbidities, death, and their lives to make the right treatment choices.
CGA can help physicians to develop a reasonable treatment plan for elderly patients, but it is time-consuming. Nowadays, a simple CGA is also used for cancer-specific geriatric assessment (CSGA), which involves 7 main aspects, including functional status, comorbidities, medication history, cognitive function, physiological status, social function and support, and nutritional status.
Postoperative adjuvant chemotherapy for colon cancer.
Adjuvant chemotherapy is mainly used for stage III and high-risk stage II colon cancer, and there are clinical concerns about drug toxicity, thus elderly patients are less likely to receive postoperative adjuvant chemotherapy. The efficacy of 5-FU/LV or capecitabine for postoperative adjuvant therapy in elderly patients is similar to that in younger patients. regimens need to be considered on an individual basis.
Adjuvant radiotherapy for rectal cancer.
The standard treatment modality for young patients with locally progressive rectal cancer is a combination of total mesorectal resection, radiotherapy and chemotherapy. The clinical concern for the benefit of combined therapy is less than the associated complications, and thus this combined treatment modality is less commonly used in older patients. Studies have shown that perioperative radiotherapy for rectal cancer reduces the risk of local recurrence and death, but the rate of non-cancer-related deaths (e.g., cardiovascular disease, radiation enteritis, hypertension, etc.) associated with radiotherapy is high. There are no results from randomized studies of perioperative radiotherapy for elderly rectal cancer, and elderly rectal cancer patients should be treated more carefully with combination therapy.
Physiological age is not a limiting factor for elderly patients not to receive curative treatment for rectal cancer, and multidisciplinary collaboration is recommended for individualized treatment of elderly patients. Combination therapy modalities that are effective in younger patients should be considered for older patients whose medical status allows it.
Palliative chemotherapy for metastatic CRC.
Metastatic CRC treatment has evolved rapidly over the past decade due to the advent of biologically targeted agents and the development of surgical techniques. Modern chemotherapy for metastatic CRC includes various active agents such as 5-FU/LV, capecitabine, irinotecan, oxaliplatin, cetuximab, bevacizumab, panitumumab, abciximab, and regifenib.
Cytotoxic chemotherapy.
Cytotoxic chemotherapy is the mainstay of treatment for metastatic CRC, and several studies have demonstrated that combination chemotherapy is effective and well tolerated in older patients. 5-FU/LV and capecitabine are the 2 most widely used agents, and they are no less well tolerated and effective in older patients than in younger patients. Irinotecan can be used in metastatic CRC, and studies have shown no effect on OS and PFS of irinotecan treatment in the elderly, but increased risk of grade 3/4 diarrhea and neutropenia should be used with caution. Studies have also confirmed that irinotecan combined with 5-FU/LV or capecitabine has superior ORR and PFS to 5-FU/LV or capecitabine treatment in both older and younger patients, and there does not appear to be a significant increase in toxicity. Oxaliplatin regimens such as FOLFOX, XELOX, or irinotecan + oxaliplatin are effective in metastatic CRC. However, the addition of oxaliplatin to the treatment of elderly patients does not seem to improve PFS, and a stop-and-go strategy can be adopted to minimize toxicity.
In conclusion, most trials have shown that the efficacy and toxicity of palliative cytotoxic therapy in older patients with metastatic CRC are similar to those in younger patients. Combination chemotherapy should be considered for older patients with good PS scores, while older patients with poor physical status can be treated with single agent or stop-and-go strategies to reduce toxicity.
Targeted therapy.
Targeted therapies significantly improve outcomes in a variety of malignancies, and studies have been conducted to evaluate the efficacy of bevacizumab, cetuximab, and panitumumab in the treatment of elderly metastatic CRC.
The addition of bevacizumab to conventional chemotherapy significantly improved PFS and OS in patients over 65 years of age, but also increased arterial thrombotic events (ATEs), with no significant increase in other toxicities. Bevacizumab in combination with capecitabine is an effective and well-tolerated regimen.
Cetuximab and panitumumab are less commonly used in first-line treatment of metastatic CRC in older patients in pilot studies and can be used alone or in combination with irinotecan to treat older patients with no less effectiveness than younger patients. Existing studies suggest that KRAS-free mutations imply higher response rates and PFS, and therefore the KRAS status needs to be clarified prior to treatment. Targeted therapy for older patients with metastatic CRC looks very promising because it is effective and less toxic than conventional cytotoxic chemotherapy. However, because targeted therapy can lead to some specific toxicities, its use should be closely monitored and toxicity detected early.
Conclusion.
Although CRC is the leading cause of cancer-related deaths in older adults, older patients are often not included in clinical trials and are inadequately staged and treated. Old age per se is not a limiting factor for adjuvant or palliative care, and treatment options are decided after careful CGA evaluation. All patients should be managed in a multidisciplinary collaborative setting and treatment should be individualized. 5-FU/LV and capecitabine benefit as adjuvant therapy for elderly stage III colon cancer as well as younger patients without increasing toxicity combination therapy remains controversial, but combination therapy modalities can be used with caution in elderly patients with locally progressive rectal cancer; combination chemotherapy can be considered for elderly patients with metastatic CRC and for frail elderly patients More studies are needed to develop evidence-based treatment guidelines for elderly CRC.