ANTINEOPLASTIC CHEMOTHERAPY OF THE OLDER CANCER PATIENT

doi:10.1016/S0889-8588(05)70284-7

Hematology/Oncology Clinics of North America

Volume 14, Issue 1, 1 February 2000, Pages 193-212

https://doi.org/10.1016/S0889-8588(05)70284-7 Get rights and content

The management of the older cancer patient with cytotoxic chemotherapy requires knowledge of the pharmacologic effects of age and awareness of the diversity of the older population.5, 6 Aging may influence several aspects of pharmacology. A progressive restriction in the functional reserve of multiple-organ systems²⁹ may alter the pharmacokinetics of antineoplastic agents and increase the susceptibility of older individuals to the complications of treatment.4, 6, 21, 23, 29, 47, 89 Cellular senescence may curtail the ability of normal tissues to repair the molecular damage caused by the drug. Older individuals may develop tumors that are more resistant to cytotoxic treatment.15, 24, 31, 64, 84

The diversity of the older population reflects the multidimensional nature of aging that mandates individualized treatment plans.5, 6, 45 To formulate and implement these plans, the practitioner needs to be experienced in assessing older individuals.

This article reviews the pharmacology of aging and offers practical suggestions for the use of chemotherapy for older individuals.

Section snippets

Pharmacokinetics

All pharmacokinetic parameters illustrated in Figure 1 are influenced by age. The absorption of drugs and nutrients is progressively reduced by restriction in the absorptive surface of the small bowel and in the splanchnic circulation.23, 29, 43, 58, 89 Lessened gastric motility and gastric secretion may also delay the absorption of drugs.23, 43 Traditionally, changes in absorption have had limited effects on cancer chemotherapy regimens, but they may become more relevant with the development

ASSESSMENT OF THE OLDER CANCER PATIENT

Treatment-related decisions must be tailored to the condition of the individual patient, based on the answers to the following questions:

1
Is the patient going to die with cancer or of cancer?
2
Is the patient going to suffer cancer-related morbidity during his or her lifetime?
3
Is the patient likely to tolerate the complications of treatment?

A comprehensive assessment of the older patient provides a frame of reference to answer these questions5, 6 and can direct treatment-related decisions.

PRACTICAL SUGGESTIONS FOR THE MANAGEMENT OF THE OLDER CANCER PATIENTS WITH CYTOTOXIC CHEMOTHERAPY

A number of practical guidelines and a research agenda for the future may be derived from this discussion.

Practical guidelines for the management of the older cancer patient with cytotoxic chemotherapy include

Pharmacologic interventions
- 1
  Adjust initial dose of chemotherapy to the renal function of the patient; subsequent doses should be further adjusted according to the nadir counts and other toxic complications.
- 2
  Maintain hemoglobin levels at or above 12 g/dL when possible with the

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Erratum: Reprint of Long-term survival and late toxicities of elderly nasopharyngeal carcinoma (NPC) patients treated by high-total- and fractionated-dose simultaneous modulated accelerated radiotherapy with or without chemotherapy (Oral Oncology (2019) 89 (40–47), (S1368837518304664) (10.1016/j.oraloncology.2018.12.008))
2019, Oral Oncology
To analyse the survival and late toxicities of elderly nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiotherapy (IMRT) with the high-total- and fractionated-dose simultaneous modulated accelerated radiation therapy (SMART) boost technique and to identify the effect of concurrent chemotherapy for these patients.
Two hundred and fifty-four elderly patients (age ≥ 60.0) with newly diagnosed non-metastatic NPC were retrospectively analysed. Statistical analyses were performed using the SPSS software program.
The actual mean total and fractionated doses delivered to the gross tumour volume of the nasopharynx (GTVnx) were 74.55 Gy and 2.49 Gy, respectively. The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) of the whole cohort were 93.0%, 85.7%, 83.2% and 74.1%, respectively. No grade 4 acute or late radiotherapy-induced toxicities were observed. Of 247 patients with stage II–IVb disease, 89 patients received radiotherapy (RT) alone, and 158 patients received concurrent chemoradiotherapy (CCRT), and the 5-year LRRFS, DMFS, DSS and OS of the RT-alone group vs. the CCRT group were 94.0% vs. 92.2%, 83.5% vs. 86.2%, 81.8% vs. 83.1% and 74.0% vs. 72.8% (all P > 0.05), respectively. Multivariate analyses showed that CCRT was not an independent predictor for LRRFS, DMFS, DSS and OS (all P > 0.05).
High-total- and fractionated-dose SMART boost IMRT could obtain a satisfactory long-term outcome with mild late toxicity in elderly NPC patients. The role of CCRT needs to be further studied to optimize the treatment strategy and improve the overall survival.
Long-term survival and late toxicities of elderly nasopharyngeal carcinoma (NPC) patients treated by high-total- and fractionated-dose simultaneous modulated accelerated radiotherapy with or without chemotherapy
2019, Oral Oncology
Citation Excerpt :
The reason for this finding may be that most of the elderly NPC patients already had poor physiologic function and low compensative capacity. When they received chemotherapy, the benefits of chemotherapy might be counteracted by its substantial impact on their normal function with numerous adverse effects [3,10–12]. Patients’ baseline health and function should be considered when considering chemotherapy, and the comparative risks and benefits should be discussed carefully [39].
Are postoperative consequences of neoadjuvant chemotherapy for non-small cell lung cancer more severe in elderly patients?
2012, Lung Cancer
The purpose of this study was to assess the postoperative morbidity of patients ≥75 years with non-small cell lung cancer (NSCLC) who underwent neoadjuvant chemotherapy, comparing them to younger patients.
We performed a case-control study over a 5-year period using Epithor, the French Society of Thoracic and Cardiovascular Surgery database, including to date more than 160,000 procedures from 103 institutions. We collected prospectively the data concerning 1510 patients with NSCLC who underwent preoperative chemotherapy, from January 2005 to December 2009. In order to compare patients with similar characteristics, we matched the 81 patients ≥75 to 81 controls (<75) for gender, American Society of Anesthesia (ASA) score, Performance Status (PS), Forced Expiratory Volume (FEV1) and histological subtype of the tumor. The patients of the control group were randomized within the 1429 patients <75 included. Lung cancer surgical treatment, post-operative morbidity and mortality rates, and length of stay (LOS) were compared between the two age groups.
There was no significant difference in type of resection between the two groups (p = 0.07): pneumonectomy 15% (n = 12) for patients ≥75 vs 28% (n = 23) for younger patients, lobectomy 65% (n = 53) vs 54% (n = 44), bilobectomy 14% (n = 11) vs 6% (n = 5) and sub-lobar resection 4% (n = 3) for the two groups. There was no significant difference in type of mediastinal lymphadenectomy (p = 0.48) between the two age groups. Elderly patients presented a more important number of postoperative complications (p = 0.04) and these ones were more severe (p = 0.03). There was no significant difference in postoperative mortality with 30-day mortality: 4.9%, n = 4, versus 2.5%, n = 2, (p = 0.83); 60-day mortality: 6.2%, n = 5, versus 2.5%, n = 2, (p = 0.61); and 90-day mortality was the same. Hospital LOS was longer for the elderly (14.9 days, CI95%[12.5;17.4] vs 11.9 days, CI95%[10.7;13.3], p < 0.001).
Postoperative morbidity after neoadjuvant chemotherapy is more important in elderly patients. These data should be taken into account when considering the interest of preoperative treatment in elderly patients with resectable NSCLC.
History of cancer and mortality in community-dwelling older adults
2011, Cancer Epidemiology
Background: The association between a history of cancer and mortality has not been studied in a propensity-matched population of community-dwelling older adults. Methods: Of the 5795 participants in the Cardiovascular Health Study, 827 (14%) had self-reported physician-diagnosed cancer at baseline. Propensity scores for cancer were used to assemble a cohort of 789 and 3118 participants with and without cancer respectively who were balanced on 45 baseline characteristics. Cox regression models were used to determine the association between cancer and all-cause mortality among matched patients, and to identify independent predictors of mortality among unmatched cancer patients. Results: Matched participants had a mean (SD) age of 74 (6) years, 57% were women, 10% were African Americans, and 38% died from all causes during 12 years of follow-up. All-cause mortality occurred in 41% and 37% of matched participants with and without a history of cancer respectively (hazard ratio when cancer was compared with no cancer, 1.16; 95% confidence interval, 1.02–1.31; P = 0.019). Among those with cancer, older age, male gender, smoking, lower than college education, fair-to-poor self-reported health, coronary artery disease, diabetes mellitus, chronic kidney disease, left ventricular hypertrophy, increased heart rate, low hemoglobin and low baseline albumin were associated with increased risk of mortality. Conclusions: Among community-dwelling older adults, a history of cancer was associated with increased mortality and among those with cancer, several socio-demographic variables and morbidities predicted mortality. These findings suggest that addressing traditional risk factors for cardiovascular mortality may help improve outcomes in older adults with a history of cancer.
The challenge of treating older patients with pancreaticobiliary malignancies
2018, Current Problems in Cancer
Pancreatic and biliary tract cancers are aggressive malignancies. They commonly present with metastatic or unresectable disease. Those that do present with resectable cancer have high rates of recurrence. Despite recent advances in surgical technique, chemotherapy, and radiotherapy regimens, they are associated with poor survival outcomes. These cancers represent an exception to the trend of improved overall survival evident in most malignancies in recent decades. Depending on the goal of treatment, active management of pancreatic and biliary cancers involves surgery, chemotherapy, and radiation therapy, either alone or in combination. Both pancreatic and biliary tract cancers have a preponderance in the older population. Older patients are a heterogeneous group; although tolerability of multimodality treatment may be a challenge for some, many fit older patients may be undertreated based on their age alone. The growing field of geriatric oncology has highlighted the importance of a comprehensive assessment of these patients, and not relying on age alone as a discriminating factor for treatment. Management of older patients with pancreaticobiliary cancers is particularly challenging owing to limited prospective data in this population. As such, there is uncertainty with regard to optimal treatment approaches for these patients. In this article, we outline the therapeutic options available to patients with localized or advanced pancreatic and biliary tract cancers, and the evidence for specified treatment options in the elderly. We examine the inclusion and outcomes of elderly patients in relevant clinical trials; the morbidity that may be encountered by elderly patients receiving specified treatments and the tools that may assist the physician in selecting elderly patients for particular treatments.
Risk stratification and beneficiary selection among elderly nasopharyngeal carcinoma patients from concurrent chemoradiotherapy combined with induction chemotherapy
2023, Cancer Medicine

View all citing articles on Scopus

: Address reprint requests to Lodovico Balducci, MD, H. Lee Moffitt Cancer Center, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, FL 33612–9497

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ANTINEOPLASTIC CHEMOTHERAPY OF THE OLDER CANCER PATIENT

Section snippets

Pharmacokinetics

ASSESSMENT OF THE OLDER CANCER PATIENT

PRACTICAL SUGGESTIONS FOR THE MANAGEMENT OF THE OLDER CANCER PATIENTS WITH CYTOTOXIC CHEMOTHERAPY

Clin Geriatr Med

Hematol Oncol Clin North Am

Arch Gerontol Ger

Hematol Oncol Clin North Am

Hematol Oncol Clin North Am

Blood

Clin Geriatr Med

Hematol Oncol Clin North Am

Blood

Blood

Cancer Treat Rev

Eur J Cancer

Am J Med

J Allergy Clin Immunol

Blood

Blood

The cardiotoxicity of chemotherapeutic drugs

Semin Oncol

Recommendations for the use of hemopoietic colony-stimulating factors: Evidence-based clinical practice guidelines

J Clin Oncol

Aggressive chemotherapy for diffuse histiocytic lymphoma in the elderly

J Am Geriatr Soc

Cancer chemotherapy in the older patient: What the medical oncologist needs to know

Cancer

Anemia of aging: A model of cancer-related anemia Cancer Control

JHLMCC

Elderly patients with aggressive non-Hodgkin's lymphoma: Disease presentation, response to treatment and survival. A Groupe d'Etude des Lymphomes de l'Adulte Study on 453 patients older than 69 years

J Clin Oncol

The treatment of elderly patients with aggressive non-Hodgkin's lymphomas: Feasibility and efficacy of an intensive multidrug regimen

Leuk Lymphoma

Cisplatin pharmacokinetics in elderly patients

Ther Drug Monit

Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetics data

Cancer Chemother Pharmacol

Treatment of acute myeloid leukemia in the older patient

Chemotherapy of metastatic breast cancer in the elderly

JAMA

Cancer pain in the elderly

Identifying hemoglobin levels for optimal Quality of Life. Results of an incremental analysis [abstract 2215]

Proceedings of the American Society of Clinical Oncology

Polypharmacy in the older patient

Cancer chemotherapy in the older patients

Depressive symptoms and three year mortality in older hospitalized medical patients

Ann Intern Med

Pharmacokinetic studies in elderly people

Clin Pharmacokinet

Biologic characteristics of primary breast cancer in the elderly

Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia

J Clin Oncol

Quality of life benefit in chemotherapy patients treated with epoietin alfa is independent of disease response or tumor type: Results from a prospective community oncology study. Procrit Study Group

J Clin Oncol

UFT plus or minus calcium folinate for metastatic colorectal cancer in older patients

Oncology (Huntingt)

Anthracyclines and anthracendiones

Physiology of aging: Relevance to symptoms, perceptions, and treatment tolerance

Relationship between cognitive impairment and early death in the elderly

BMJ

Apoptosis, chemotherapy and aging

Once weekly dosing of epoietin alfa is similar to three-times weekly dosing in increasing hemoglobin and quality of life

Proceedings of the American Society of Clinical Oncology

Cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy in women more than 65 years old with advanced breast cancer. The elimination of age trends in toxicity by using doses based on creatinine clearance

J Clin Oncol

Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin

J Clin Oncol

Impact of therapy with epoietin alfa on clinical outcomes in patients with non-myeloid malignancies during cancer chemotherapy in community oncology practice

J Clin Oncol

Elderly patients with aggressive non-Hodgkin's lymphoma treated with CHOP chemotherapy plus granulocyte-macrophage colony-stimulating factor: Identification of two age subgroups with differing hematologic toxicity

J Clin Oncol