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Evidence suggests that appropriately selected older adults can tolerate standard-dose chemotherapy and achieve survival outcomes comparable to younger patients. However, older adults are usually under-represented in clinical trials and often receive reduced doses of chemotherapy due to concerns regarding age-related frailty, polypharmacy, and toxicity.
This study seeks to evaluate chemotherapy dosing patterns and associated survival outcomes in older patients.
Lung cancer remains the leading cause of cancer-related mortality globally, responsible for approximately 1.8 million deaths annually. Non-small cell lung cancer (NSCLC) comprises about 85% of all lung cancer cases, with adenocarcinoma (ADC) now the predominant histological subtype. In Malaysia, NSCLC is similarly the most common form of lung cancer, with high proportions of EGFR and ALK mutations in certain subgroups.
Despite the emergence of targeted therapy and immunotherapy, cytotoxic chemotherapy, particularly platinum-based doublets remains the backbone of treatment for many NSCLC patients lacking actionable mutations. These patients often present with advanced disease and limited survival prospects, with median overall survival (OS) of 8- 10 months. These includes older patients with advanced NSCLC and no actionable mutations who depend on chemotherapy for disease control.
Clinical decisions regarding dosing are frequently influenced by perceptions of frailty rather than individual fitness. Evidence suggests that appropriately selected older adults can tolerate standard-dose chemotherapy and achieve survival outcomes comparable to younger patients. However, older adults are usually under-represented in clinical trials and often receive reduced doses of chemotherapy due to concerns regarding age-related frailty, polypharmacy, and toxicity. This raises an important question: does dose reduction compromise survival outcomes in older NSCLC patients?
This study seeks to address this knowledge gap by retrospectively evaluating chemotherapy dosing patterns and associated survival outcomes in older patients treated at three centres in Malaysia: Universiti Malaya Medical Centre (UMMC), Hospital Tengku Ampuan Afzan, Kuantan and Hospital Wanita dan Kanak-kanak, Likas, Sabah and one centre in Hong Kong: Queen Mary Hospital, The University of Hong Kong. It will evaluate whether chemotherapy dose reductions are associated with poorer survival outcomes in older NSCLC patients. It will also assess clinical predictors such as ECOG performance status, BMI, comorbidities, and gender to identify factors influencing treatment tolerance and survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal dose group | Patients receiving standard dose of chemotherapy |
| |
| Dose reduction group | Patients receiving lower doses of chemotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Progression free survival | Other | PFS |
| |
| Measure | Description | Time Frame |
|---|---|---|
| To compare the overall survival (OS) between older NSCLC patients treated with standard-dose versus reduced-dose first-line platinum-doublet chemotherapy OR single agent non-platinum chemotherapy. | From enrollment to the end of study on 31 Dec 2026 |
| Measure | Description | Time Frame |
|---|---|---|
| To compare the progression free survival (PFS) between older NSCLC patients treated with standard-dose versus reduced-dose first-line platinum-doublet chemotherapy OR single agent non-platinum chemotherapy. | From enrollment to end of study on 31 Dec 2026 | |
| To assess objective response rates in patients who complete FOUR cycles of chemotherapy. |
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Inclusion Criteria:
Exclusion Criteria:
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Retrospective cohort study using data from three centres in Malaysia from 2020 to 2025. All patients aged ≥65 years with advanced/metastatic NSCLC and no actionable driver mutations who received AT LEAST ONE CYCLE of first-line chemotherapy will be included in the analysis.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mau Ern Poh, MBBS | Contact | +60379494422 | ernestpoh@um.edu.my | |
| Danouska Bala Krishnan | Contact | +603-79492351 | danouska@ummc.edu.my |
| Name | Affiliation | Role |
|---|---|---|
| Mau Ern Poh, MBBS | University of Malaya | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Queen Mary Hospital, The University of Hong Kong | Recruiting | Hong Kong | Hong Kong |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27229180 | Background | Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA Jr, Mok TS, Hirsch FR. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016. J Thorac Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May 23. | |
| 25470694 |
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| Overall survival |
| Other |
OS |
|
| From enrollment to end of study period on 31 Dec 2026 |
| Hospital Tengku Ampuan Afzan | Recruiting | Kuantan | Pahang | Malaysia |
|
| Hospital Wanita dan Kanak-Kanak Sabah | Recruiting | Kota Kinabalu | Sabah | Malaysia |
|
| Universiti Malaya Medical Centre | Recruiting | Kuala Lumpur | Malaysia |
|
| Background |
| Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440. |
| 19692680 | Background | Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19. |
| Background | 7. Sedrak MS, Sun CL, Liu X, et al. Aging and tolerance to chemotherapy: Impact of dose reduction and treatment delays on survival outcomes. Journal of Clinical Oncology, 2021 39, 1714-1723. |
| 15224973 | Background | Hurria A, Kris MG. Management of lung cancer in older adults. CA Cancer J Clin. 2003 Nov-Dec;53(6):325-41. doi: 10.3322/canjclin.53.6.325. |
| 16192578 | Background | Maione P, Perrone F, Gallo C, Manzione L, Piantedosi F, Barbera S, Cigolari S, Rosetti F, Piazza E, Robbiati SF, Bertetto O, Novello S, Migliorino MR, Favaretto A, Spatafora M, Ferrau F, Frontini L, Bearz A, Repetto L, Gridelli C, Barletta E, Barzelloni ML, Iaffaioli RV, De Maio E, Di Maio M, De Feo G, Sigoriello G, Chiodini P, Cioffi A, Guardasole V, Angelini V, Rossi A, Bilancia D, Germano D, Lamberti A, Pontillo V, Brancaccio L, Renda F, Romano F, Esani G, Gambaro A, Vinante O, Azzarello G, Clerici M, Bollina R, Belloni P, Sannicolo M, Ciuffreda L, Parello G, Cabiddu M, Sacco C, Sibau A, Porcile G, Castiglione F, Ostellino O, Monfardini S, Stefani M, Scagliotti G, Selvaggi G, De Marinis F, Martelli O, Gasparini G, Morabito A, Gattuso D, Colucci G, Galetta D, Giotta F, Gebbia V, Borsellino N, Testa A, Malaponte E, Capuano MA, Angiolillo M, Sollitto F, Tirelli U, Spazzapan S, Adamo V, Altavilla G, Scimone A, Hopps MR, Tartamella F, Ianniello GP, Tinessa V, Failla G, Bordonaro R, Gebbia N, Valerio MR, D'Aprile M, Veltri E, Tonato M, Darwish S, Romito S, Carrozza F, Barni S, Ardizzoia A, Corradini GM, Pavia G, Belli M, Colantuoni G, Galligioni E, Caffo O, Labianca R, Quadri A, Cortesi E, D'Auria G, Fava S, Calcagno A, Luporini G, Locatelli MC, Di Costanzo F, Gasperoni S, Isa L, Candido P, Gaion F, Palazzolo G, Nettis G, Annamaria A, Rinaldi M, Lopez M, Felletti R, Di Negro GB, Rossi N, Calandriello A, Maiorino L, Mattioli R, Celano A, Schiavon S, Illiano A, Raucci CA, Caruso M, Foa P, Tonini G, Curcio C, Cazzaniga M. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study. J Clin Oncol. 2005 Oct 1;23(28):6865-72. doi: 10.1200/JCO.2005.02.527. |
| 11773167 | Background | Sundararajan V, Hershman D, Grann VR, Jacobson JS, Neugut AI. Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study. J Clin Oncol. 2002 Jan 1;20(1):173-8. doi: 10.1200/JCO.2002.20.1.173. |
| Background | 3. Liam, Chong-Kin, Toh-Yoon Evelyn Goh, Nur Syafikah Shamsudin, and Chee-Chee Khoo. 2022. "Driver Gene Alterations and PD-L1 Expression in Non-Small Cell Lung Cancer and Their Association with Smoking and Gender in a Malaysian Population." Asian Pacific Journal of Cancer Prevention 23 (6): 1911-1917. |
| 21810685 | Background | Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S, Hansen K, Ramani R, Lachs M, Wong FL, Tew WP. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011 Sep 1;29(25):3457-65. doi: 10.1200/JCO.2011.34.7625. Epub 2011 Aug 1. |
| 24134505 | Background | Hamaker ME, Schiphorst AH, ten Bokkel Huinink D, Schaar C, van Munster BC. The effect of a geriatric evaluation on treatment decisions for older cancer patients--a systematic review. Acta Oncol. 2014 Mar;53(3):289-96. doi: 10.3109/0284186X.2013.840741. Epub 2013 Oct 17. |
| ID | Term |
|---|---|
| D000077982 | Progression-Free Survival |
| ID | Term |
|---|---|
| D016896 | Treatment Outcome |
| D011379 | Prognosis |
| D003933 | Diagnosis |
| D016019 | Survival Analysis |
| D013223 | Statistics as Topic |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D017063 | Outcome Assessment, Health Care |
| D010043 | Outcome and Process Assessment, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017531 | Health Care Evaluation Mechanisms |
| D017530 | Health Care Quality, Access, and Evaluation |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
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