Can we avoid the toxicity of chemotherapy in elderly cancer patients?

Feliú, Jaime; Heredia-Soto, Victoria; Gironés, Regina; Jiménez-Munárriz, Beatriz; Saldaña, Juana; Guillén‐Ponce, Carmen; Molina‐Garrido, María‐José

doi:10.1016/j.critrevonc.2018.08.008

Cited by 35 publications

(31 citation statements)

References 69 publications

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“…Although chronological old age alone does not always reflect an intolerability to systemic cytotoxic chemotherapy in patients with cancer, in older adults, a functional decline of their major organs, including the intestines, liver, and kidneys, and comorbid illness of these major organs may cause a vulnerability to serious adverse reactions following systemic cytotoxic chemotherapy compared with younger patients [ 6 ]. Pharmacokinetic implications such as “a decline in renal function” should be distinguished from pharmacodynamic characteristics such as “a decline in bone marrow”.…”

Section: Discussionmentioning

confidence: 99%

“…Although numeric age alone does not reflect a tolerability to cytotoxic chemotherapy, older adults with cancer are generally considered to be more vulnerable to the adverse effects of systemic chemotherapy than younger patients. This may be because older adults may have a decline in function of their major organs, such as the kidneys, liver, and bone marrow and physiological changes of decreased muscle mass and more chances of comorbid illness [ 6 ]. When planning the schedules and doses of systemic chemotherapy before the administration of chemotherapeutics, physicians must consider the goal of treatment (curative intent, such as neoadjuvant or adjuvant chemotherapy or palliation), drug sensitivity, tumor burden and biology, characteristics and toxicities of chemotherapeutic agents, performance status, and concomitant disease, in addition to the age of the patient.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study

Hwang

Kwon

Kim

et al. 2021

Cancers

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Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4–47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3–5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study

Hwang

Kwon

Kim

et al. 2021

Cancers

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“…Pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging and secondarily, increase the treatment toxicity [5]. Other factors such as comorbidities and polypharmacy could also increase the risk of toxicity and interactions [6].…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer

Tuca

Gallego

Ghanem

et al. 2020

JCM

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Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk comes from the fact that pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging. Although the chemotherapy efficacy in metastatic colorectal cancer (mCRC) is similar for older and young patients, more toxicity is presented in the elderly. While the mono-chemotherapy provides the same benefit for young and older patients, doublets front-line chemotherapy improves progression-free survival (PFS) but not overall survival (OS) in the elderly. Furthermore, the benefit of the addition of bevacizumab to chemotherapy in older patients has been shown in several clinical trials, while the clinical data for the benefit of anti-epidermal growth factor antibodies are scarcer. Immunocheckpoint inhibitors could be an appropriate option for patients with microsatellite instability (MSI) tumors. A prior geriatric assessment is required before deciding the type of treatment in order to offer the best therapeutic option.

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“…In clinical trials, patient populations are selected with limited or no comorbidities and concurrent medications are not permitted, follow-up period is much narrower, and the toxicities are detected earlier, so patient populations enrolled may not accurately represent the general oncology population [21]. Multiple drug therapy is also common in patients with cancer to treat their cancer or to manage the adverse effects and comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Effect of capmatinib on the pharmacokinetics of digoxin and rosuvastatin administered as a two-drug cocktail in patients with MET-dysregulated advanced solid tumors: A phase I, multicenter, open-label, single-sequence drug-drug interaction study

Grande¹,

Giovannini²,

Marrière³

et al. 2020

Preprint

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Aims Capmatinib, an orally bioavailable, highly potent and selective MET inhibitor, was recently approved to treat adult patients with metastatic non-small cell lung cancer with METex14 skipping mutations. The study investigated the effect of capmatinib on the pharmacokinetics of a single oral dose of digoxin and rosuvastatin, administered orally as a two-drug cocktail in patients with MET-dysregulated advanced solid tumors. Methods This was a multicenter, open-label, single-sequence study. An oral drug cocktail containing 0.25 mg digoxin and 10 mg rosuvastatin was administered to adult patients with METdysregulated advanced solid tumors on Day 1, and then on Day 22 with capmatinib. Between Days 11 and 32, capmatinib 400 mg was administered twice daily to ensure the attainment of steady state for drug-drug interaction (DDI) assessment. Pharmacokinetics of cocktail drugs and safety of capmatinib were evaluated. Results Thirty-two patients (median age: 61.5 years) were enrolled. Co-administration of capmatinib increased digoxin Cmax, and AUC inf by 74%, and 47%, respectively. Co-administration of capmatinib increased rosuvastatin Cmax, and AUC inf by 204%, and 108%, respectively. Most frequent adverse events (AEs; [?]25% for all grades) were nausea (56.3%), asthenia (43.8%), constipation and vomiting (40.6%, each), peripheral edema (28.1%) and pyrexia (25%). Most frequent Grade 3/4 AEs ([?]5%) were anemia and pulmonary embolism (9.4%, each), asthenia, dyspnea, nausea and vomiting (6.3%, each). Conclusion This study demonstrated that capmatinib is an inhibitor of P-gp as well as BCRP transporters, with clinically relevant DDI potential. Capmatinib was well-tolerated and no unexpected safety concerns were observed.

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Can we avoid the toxicity of chemotherapy in elderly cancer patients?

Cited by 35 publications

References 69 publications

Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study

Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study

Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer

Effect of capmatinib on the pharmacokinetics of digoxin and rosuvastatin administered as a two-drug cocktail in patients with MET-dysregulated advanced solid tumors: A phase I, multicenter, open-label, single-sequence drug-drug interaction study

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