Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design

Rohit Lal, Nawel Bourayou, Gunnar Hillerdal, Marianne Nicolson, Anders Vikstrom, Maria Lorenzo, Yulia D'yachkova, Susana Barriga, Carla Visseren-Grul, Rohit Lal, Nawel Bourayou, Gunnar Hillerdal, Marianne Nicolson, Anders Vikstrom, Maria Lorenzo, Yulia D'yachkova, Susana Barriga, Carla Visseren-Grul

Abstract

Background: Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting.

Methods: Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0-1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m(2) every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients' quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011.

Discussion: This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design requires unusual methodology and specific logistics to address outcomes relevant to the home-delivery approach. This article presents a study design that offers a novel and reproducible model for home-based chemotherapy, and provides an up-to-date overview of the literature regarding this type of treatment.

Trial registration: ClinicalTrials.gov: NCT01473563.

Figures

Figure 1
Figure 1
Study design.

References

    1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18(3):581–592.
    1. D’Addario G, Früh M, Reck M, Baumann P, Klepetko W, Felip E. ESMO guidelines working group. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):116–119.
    1. Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E. on behalf of the ESMO Guidelines Working Group. Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vi56–vii64.
    1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer. V.3. 2012. .
    1. Azzoli CG, Baker S Jr, Temin S, Pao W, Aliff T, Brahmer J, Johnson DH, Laskin JL, Masters G, Milton D, Nordquist L, Pfister DG, Piantadosi S, Schiller JH, Smith R, Smith TJ, Strawn JR, Trent D, Giaccone G. American society of clinical oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2009;27(36):6251–6266. doi: 10.1200/JCO.2009.23.5622.
    1. Azzoli CG, Temin S, Giaccone G. 2011 Focused update of 2009 American society of clinical oncology clinical practice guideline update on chemotherapy for stage IV Non-small-cell lung cancer. J Oncol Pract. 2012;8(1):63–66. doi: 10.1200/JOP.2011.000374.
    1. Coudert B, Ciuleanu T, Park K, Wu YL, Giaccone G, Brugger W, Gopalakrishna P, Cappuzzo F. SATURN Investigators. Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy. Ann Oncol. 2012;23(2):388–394. doi: 10.1093/annonc/mdr125.
    1. Department of Health. Cancer reform strategy. 2007. .
    1. Anderson H, Addington-Hall JM, Peake MD, McKendrik J, Keane K, Thatcher N. Domiciliary chemotherapy with gemcitabine is safe and acceptable to advanced non-small-cell lung cancer patients: results of a feasibility study. Br J Cancer. 2003;89(12):2190–2196. doi: 10.1038/sj.bjc.6601420.
    1. Bazian Ltd. Home chemotherapy. A review of recent published research evidence reporting the success, safety and acceptability of adult chemotherapy delivered at home compared to hospital outpatient delivered services. London: Bazian Ltd; 2010.
    1. Borras JM, Sanchez-Hernandez A, Navarro M, Martinez M, Mendez E, Ponton JL, Espinas JA, Germa JR. Compliance, satisfaction, and quality of life of patients with colorectal cancer receiving home chemotherapy or outpatient treatment: a randomised controlled trial. BMJ. 2001;322(7290):826. doi: 10.1136/bmj.322.7290.826.
    1. King MT, Hall J, Caleo S, Gurney HP, Harnett PR. Home or hospital? An evaluation of the costs, preferences, and outcomes of domiciliary chemotherapy. Int J Health Serv. 2000;30(3):557–579. doi: 10.2190/CY03-EV15-K38Y-X4AA.
    1. Rischin D, White MA, Matthews JP, Toner GC, Watty K, Sulkowski AJ, Clarke JL, Buchanan L. A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis. Med J Aust. 2000;173(3):125–127.
    1. Stockelberg D, Lehtola P, Norén I. Palliative treatment at home for patients with haematological disorders. Support Care Cancer. 1997;5(6):506–508. doi: 10.1007/s005200050121.
    1. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543–3551. doi: 10.1200/JCO.2007.15.0375.
    1. Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589–1597. doi: 10.1200/JCO.2004.08.163.
    1. Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009;374(9699):1432–1440. doi: 10.1016/S0140-6736(09)61497-5.
    1. Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: final overall survival results of the phase III study of maintenance Pemetrexed versus placebo immediately after induction treatment with Pemetrexed plus cisplatin for advanced nonsquamous Non-small-cell lung cancer. J Clin Oncol. 2013;31(23):2895–2902. doi: 10.1200/JCO.2012.47.1102.
    1. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 1982;5:649–655. doi: 10.1097/00000421-198212000-00014.
    1. Eisenhauer EA, Therasse P, Bogaert J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45(2):228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging handbook: from the AJCC cancer staging manual 7th edition. New York: Springer; 2009.
    1. EuroQol Group. EuroQol – a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208.
    1. Hollen PJ, Gralla RJ, Kris MG, Cox C, Belani CP, Grunberg SM, Crawford J, Neidhart JA. Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Cancer. 1994;73(8):2087–2098. doi: 10.1002/1097-0142(19940415)73:8<2087::AID-CNCR2820730813>;2-X.
    1. US Department Of Health And Human Services. Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. NIH; 2009. .
    1. Collett D. Modelling survival data in medical research. 1. London: Chapman & Hall; 1994.
    1. Department of Health Cancer Policy Team. Chemotherapy services in the community. A guide for PCTs, 2010. 2010. .
    1. Haute Autorité de Santé. In-hospital and at-home cancer chemotherapy: a comparison of costs and organisation of care. France: Saint-Denis; 2005. Health economic assessment.
    1. Abenhaim L, Louvard D. Rapport de la commission d’orientation sur le cancer. (In French) Paris: Ministère de la Santé, de la Famille et des Personnes handicapées; 2003.
    1. Aligon A, Com-Ruelle L, Renaud T, Lebrun E. Centre de Recherche d’Etude et de Documentation en Economie de la Santé (CREDES): Évaluation du coût de la prise en charge en hospitalisation à domicile. (In French) Paris: CREDES; 2003.
    1. Agence Nationale d’Accréditation et d’Évaluation en Santé (ANAES) Consensus formalise. Critères d’éligibilité des patients à une chimiothérapie anticancéreuse à domicile. Recommandations. (In French) France: Saint-Denis La Plaine; 2003. .
    1. Gridelli C, Maione P, Rossi A, Bareschino MA, Schettino C, Sacco PC, Zeppa R. Pemetrexed in advanced non-small cell lung cancer. Expert Opin Drug Saf. 2011;10(2):311–317. doi: 10.1517/14740338.2011.553281.
    1. Gridelli C, de Marinis F, Pujol JL, Reck M, Ramlau R, Parente B, Pieters T, Middleton G, Corral J, Winfree K, Melemed S, Zimmermann A, John W, Beyrer J, Chouaki N, Visseren-Grul C, Paz-Ares LG. Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2012;7(11):1713–1721. doi: 10.1097/JTO.0b013e318267cf84.
    1. Belani CP, Brodowicz T, Ciuleanu TE, Krzakowski M, Yang SH, Franke F, Cucevic B, Madhavan J, Santoro A, Ramlau R, Liepa AM, Visseren-Grul C, Peterson P, John WJ, Zielinski CC. Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study. Lancet Oncol. 2012;13(3):292–299. doi: 10.1016/S1470-2045(11)70339-4.
    1. Borner MM, Schoffski P, de Wit R, Caponigro F, Comella G, Sulkes A, Greim G, Peters GJ, van der Born K, Wanders J, de Boer RF, Martin C, Fumoleau P. Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer. 2002;38(3):349–358. doi: 10.1016/S0959-8049(01)00371-9.
    1. Brown DF, Muirhead MJ, Travis PM, Vire SR, Weller J, Hauer-Jensen M. Mode of chemotherapy does not affect complications with an implantable venous access device. Cancer. 1997;80(5):966–972. doi: 10.1002/(SICI)1097-0142(19970901)80:5<966::AID-CNCR20>;2-T.
    1. Collichio FA, Amamoo MA, Fogleman J, Griggs J, Graham M. Phase II study of low-dose infusional 5-fluorouracil and paclitaxel (Taxol) given every 2 weeks in metastatic breast cancer. Am J Clin Oncol. 2002;25(2):194–197. doi: 10.1097/00000421-200204000-00020.
    1. Inaba Y, Yamaura H, Sato Y, Najima M, Shimamoto H, Nishiofuku H, Ura T, Muro K. Central venous access port-related complications in outpatient chemotherapy for colorectal cancer. Jpn J Clin Oncol. 2007;37(12):951–954. doi: 10.1093/jjco/hym118.
    1. Lowenthal RM, Piaszczyk A, Arthur GE, O’Malley S. Home chemotherapy for cancer patients: cost analysis and safety. Med J Aust. 1996;165(4):184–187.
    1. Malone J, Kavanagh J, Crosson K, Streckfuss B. Domiciliary chemotherapy for malignant disease. Eur J Gynaecol Oncol. 1986;7(2):120–121.
    1. Nanninga AG, De Vries EG, Willemse PH, Oosterhuis BE, Sleijfer DT, Hoekstra HJ, Mulder NH. Continuous infusion of chemotherapy on an outpatient basis via a totally implanted venous access port. Eur J Cancer. 1991;27(2):147–149. doi: 10.1016/0277-5379(91)90474-R.
    1. Pfeiffer P, Mortensen JP, Bjerregaard B, Eckhoff L, Schonnemann K, Sandberg E, Aabo K, Jakobsen A. Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer. Eur J Cancer. 2006;42(16):2738–2743. doi: 10.1016/j.ejca.2006.06.027.
    1. Ron IG, Lotan A, Inbar MJ, Chaitchik S. Advanced colorectal carcinoma: redefining the role of oral ftorafur. Anticancer Drugs. 1996;7(6):649–654. doi: 10.1097/00001813-199608000-00005.
    1. Tokars JI, Cookson ST, McArthur MA, Boyer CL, McGeer AJ, Jarvis WR. Prospective evaluation of risk factors for bloodstream infection in patients receiving home infusion therapy. Ann Intern Med. 1999;131(5):340–347. doi: 10.7326/0003-4819-131-5-199909070-00004.
    1. Twelves C, Gollins S, Grieve R, Samuel L. A randomised cross-over trial comparing patient preference for oral capecitabine and 5-fluorouracil/leucovorin regimens in patients with advanced colorectal cancer. Ann Oncol. 2006;17(2):239–245.
    1. Vokes EE, Schilsky RL, Choi KE, Magid DM, Guarnieri CM, Whaling SM, Ratain MJ, Weichselbaum RR, Panje WR. A randomized study of inpatient versus outpatient continuous infusion chemotherapy for patients with locally advanced head and neck cancer. Cancer. 1989;63(1):30–36. doi: 10.1002/1097-0142(19890101)63:1<30::AID-CNCR2820630105>;2-M.

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