Pharmacy World & Science

, Volume 31, Issue 1, pp 1–13 | Cite as

Stability of antineoplastic agents in use for home-based intravenous chemotherapy

  • Frédéric BenizriEmail author
  • Brigitte Bonan
  • Anne-Laure Ferrio
  • Marie-Laure Brandely
  • Vincent Castagné
  • Nathalie Théou-Anton
  • Muriel Verlinde-Carvalho
  • Laurent Havard
Review Article


Aim of the review The aim of this work was first to define which antineoplastic agents with sufficiently long stability could be eligible in the circuit of home-based therapy (centralised preparation, transport to the patient’s home and administration by nurses) and, second, to propose a standardisation of the stability data of anticancer drugs in use for home hospitalisation. Method A survey carried out in six hospital pharmacies of the Assistance Publique—Hôpitaux de Paris (AP-HP) hospitals, with important activity in oncology, listed the stability data used locally by each site. The final goal is to reach a consensus for the stability of cytotoxic drugs, which was the result of an original collaboration between the pharmacists of the compounding unit and the quality control unit. These results were compared to marketing authorisation data. Results The survey showed that eight antineoplastic agents of 34 were prepared under identical conditions (infusion diluent, concentration range, protection from light, temperature) by all hospitals (3 ≤ n ≤ 6): the stability was identical between each site for only two cytotoxic drug preparations (fotemustine and gemcitabine) and varied by up to 168 h or 7 days for the preparations of dacarbazine, epirubicine and cisplatin. Stability validated by pharmacists and those provided by marketing authorisation ranged respectively from “extemporaneously prepared” at 1,344 h (median = 168 h) to “extemporaneously prepared” at 720 h (median = 4 h). For 11 antineoplastic drugs, no information about the stability after compounding was specified in the marketing authorisation. Of all cytotoxic drugs used in the Hospital at Home of AP-HP, stability after compounding validated by pharmacists was less than 30 h for six of them, between 30 and 78 h for four and exceeding 78 h for the remaining 24. Conclusion Considering the lack of data about cytotoxic drugs stability provided by the pharmaceutical companies and the difficulties in retrieving and interpreting the literature data, a consensus on the stability of cytotoxic drug preparations is essential for the current practice. With this approach, initiated for home hospitalisation, we propose in this study an initiative of the standardisation of stability data which offers a decision support for other centres.


Antineoplastic agents Centralised preparation units Decision support Home-based chemotherapy Pharmaceutical manufacturers Stability Standardisation 



We would like to acknowledge the working group of hospital pharmacists for their involvement in this work: Louis Joyeux (Hospital at Home, AP-HP, Paris), Nathalie Leguyader (Armand Trousseau, AP-HP, Paris), Isabelle Madelaine-Chambrin (Saint Louis, AP-HP, Paris), Nicole Poisson (AGEPS, AP-HP, Paris), Delphine Pozzi (Raymond Poincaré, AP-HP, Garches), Patrice Prognon (HEGP, AP-HP, Paris), Marie Savet (Robert Debré, AP-HP, Paris).

Conflicts of interest

The authors declare no conflicts of interest directly relevant to the content of this manuscript.


No funding was received.


  1. 1.
    Borras JM, Sanchez-Hernandez A, Navarro M, Martinez M, Mendez E, Ponton JLL, et al. 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.PubMedCrossRefGoogle Scholar
  2. 2.
    Rischin D, White MA, Matthews JP, Toner GC, Watty K, Sulkowski AJ, et al. A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis. Med J Aust. 2000;173(3):125–7.PubMedGoogle Scholar
  3. 3.
    Lowenthal RM, Piaszczyk A, Arthur GE, O’Malley S. Home chemotherapy for cancer patients: cost analysis and safety. Med J Aust. 1996;165(4):184–7.PubMedGoogle Scholar
  4. 4.
    King MT, Hall JP, Harnett PR. A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis. Med J Aust 2001;174(6):312; author reply 312–3.PubMedGoogle Scholar
  5. 5.
    Raphaël R, Yves D, Giselle C, Magali M, Odile CM. Cancer treatment at home or in the hospital: what are the costs for French public health insurance? Findings of a comprehensive-cancer centre. Health Policy. 2005;72(2):141–8. doi: 10.1016/j.healthpol.2004.07.001.PubMedCrossRefGoogle Scholar
  6. 6.
    Vergnenègre A, Decroisette C, Vincent F, Dalmay F, Melloni B, Bonnaud F, et al. Economic analysis of home based versus hospital outpatient chemotherapy in stage IV non small cell lung cancer. Rev Mal Respir. 2006;23(3 Pt 1):255–63. doi: 10.1016/S0761-8425(06)71575-3.PubMedGoogle Scholar
  7. 7.
    The French National Cancer Institute. Plan cancer 2003–2007. Mission interministérielle pour la lutte contre le cancer. Available online at:
  8. 8.
    Circulaire interministérielle DHOS/SDO/2005/101 du 22 février 2005 relative à l’organisation des soins en cancérologie NOR: SANH0530076C. Available online at:
  9. 9.
    Haute Autorité de Santé. Practice guidelines: patient selection criteria for at-home cancer chemotherapy—formal consensus. September 2003. Available online at:
  10. 10.
    Beijnen JH. Home-based chemotherapy confronts pharmacists with stability and compatibility problems. Pharm Weekbl Sci. 1992;14(6):337. doi: 10.1007/BF01970167.PubMedGoogle Scholar
  11. 11.
    American Society of Health-System Pharmacy. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm. 2006;(63):1172–91. Available online at:
  12. 12.
    Agence Française de Sécurité Sanitaire des Produits de Santé. Bonnes pratiques de préparation. 3 Décembre 2007. Available online at:
  13. 13.
    National Institute for Occupational Safety and Health. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. NIOSH Publication September 2004;165. Available online at:
  14. 14.
    Beijnen JH, Vendrig DE, Underberg WJ. Stability of vinca alkaloid anticancer drugs in three commonly used infusion fluids. J Parenter Sci Technol. 1989;43(2):84–7.PubMedGoogle Scholar
  15. 15.
    Beitz C, Bertsch T, Hannak D, Schrammel W, Einberger C, Wehling M. Compatibility of plastics with cytotoxic drug solutions—comparison of polyethylene with other container materials. Int J Pharm. 1999;185(1):113–21. doi: 10.1016/S0378-5173(99)00175-1.PubMedCrossRefGoogle Scholar
  16. 16.
    De Vroe C, De Muynck C, Remon JP, Samsom M. A study on the stability of three antineoplastic drugs and on their sorption by i.v. delivery systems and end-line filters. Int J Pharm. 1990;65:49–56. doi: 10.1016/0378-5173(90)90008-R.CrossRefGoogle Scholar
  17. 17.
    Girona V, Prat J, Pujol M, Muñoz M. Stability of vinblastine sulphate in 0.9% sodium chloride in polypropylene syringes. Boll Chim Farm. 1996;135(7):413–4.PubMedGoogle Scholar
  18. 18.
    Quebbeman EJ, Hoffman NE, Ausman RK, Hamid AA. Stability of mitomycin admixtures. Am J Hosp Pharm. 1985;42(8):1750–4.PubMedGoogle Scholar
  19. 19.
    Walker SE, Milliken D, Law S. Stability of bortezomib reconstituted with 0.9% sodium chloride at 4°C and room temperature (23°C). CJHP. 2008;61(1):14–20.Google Scholar
  20. 20.
    Li WY, Koda RT. Stability of irinotecan hydrochloride in aqueous solutions. Am J Health Syst Pharm. 2002;59(6):539–44.PubMedGoogle Scholar
  21. 21.
    Jacolot A, Arnaud P, Lecompte D, Alamercery S, Caroff E, Naveau C, et al. Stability and compatibility of 2.5 mg/ml methotrexate solution in plastic syringes over 7 days. Int J Pharm. 1996;128:283–6. doi: 10.1016/0378-5173(95)04242-3.CrossRefGoogle Scholar
  22. 22.
    Rondelot G, Serrurier C, Vigneron J, Zenier H, May I, Demoré B. Stability of pemetrexed 25 mg/mL in a glass vial and 5 mg/mL stored in a PVC container after storage for one month at 2–8°C. EJHP Sci. 2007;13(1):14–6.Google Scholar
  23. 23.
    Craig SB, Bhatt UH, Patel K. Stability and compatibility of topotecan hydrochloride for injection with common infusion solutions and containers. J Pharm Biomed Anal. 1997;16(2):199–205. doi: 10.1016/S0731-7085(97)00022-8.PubMedCrossRefGoogle Scholar
  24. 24.
    Dine T, Lebegue S, Benaji B, Gressier B, Segard V, Goudaliez F, et al. Stability and compatibility studies of four cytostatic agents (fluorouracil, dacarbazine, cyclophosphamide and ifosfamide) with PVC infusion bags. Pharm Sci Commun. 1994;4:97–101.Google Scholar
  25. 25.
    Vigneron J. Stability studies of drugs used in oncology: the role of the hospital pharmacist. EJHP Pract. 2006;12(6):75–6.Google Scholar
  26. 26.
    de Lemos ML, Hamata L. Stability issues of parenteral chemotherapy drugs. J Oncol Pharm Pract. 2007;13(1):27–31. doi: 10.1177/1078155206075236.PubMedCrossRefGoogle Scholar
  27. 27.
    Koberda M, Zieske PA, Raghavan NV, Payton RJ. Stability of bleomycin sulfate reconstituted in 5% dextrose injection or 0.9% sodium chloride injection stored in glass vials or polyvinyl chloride containers. Am J Hosp Pharm. 1990;47(11):2528–9.PubMedGoogle Scholar
  28. 28.
    André P, Cisternino S, Chiadmi F, Toledano A, Schlatter J, Fain O, et al. Stability of bortezomib 1-mg/mL solution in plastic syringe and glass vial. Ann Pharmacother. 2005;39(9):1462–6. doi: 10.1345/aph.1E620.PubMedCrossRefGoogle Scholar
  29. 29.
    Benaji B, Dine T, Luyckx M, Brunet C, Goudaliez F, Mallevais ML, et al. Stability and compatibility of cisplatin and carboplatin with PVC infusion bags. J Clin Pharm Ther. 1994;19(2):95–100. doi: 10.1111/j.1365-2710.1994.tb01118.x.PubMedCrossRefGoogle Scholar
  30. 30.
    Daouphars M, Vigneron J, Perrin A, Hoffman MA. Stability of cladribine in either polyethylene containers or polyvinyl chloride bags. EJHP Sci. 1997;3(4):154–6.Google Scholar
  31. 31.
    Beijnen JH, van Gijn R, Challa EE, Kaijser GP, Underberg WJ. Chemical stability of two sterile, parenteral formulations of cyclophosphamide (Endoxan) after reconstitution and dilution in commonly used infusion fluids. J Parenter Sci Technol. 1992;46(4):111–6.PubMedGoogle Scholar
  32. 32.
    El Aatmani M, Poujol S, Astre C, Malosse F, Pinguet F. Stability of dacarbazine in amber glass vials and polyvinyl chloride bags. Am J Health Syst Pharm. 2002;59(14):1351–6.PubMedGoogle Scholar
  33. 33.
    Wood MJ, Irwin WJ, Scott DK. Stability of doxorubicin, daunorubicin and epirubicin in plastic syringes and minibags. J Clin Pharm Ther. 1990;15(4):279–89. doi: 10.1111/j.1365-2710.1990.tb00386.x.PubMedCrossRefGoogle Scholar
  34. 34.
    Thiesen J, Krämer I. Physico-chemical stability of docetaxel premix solution and docetaxel infusion solutions in PVC bags and polyolefine containers. Pharm World Sci. 1999;21(3):137–41. doi: 10.1023/A:1008644801096.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang Y, Trissel LA. Physical and chemical stability of etoposide phosphate solutions. J Am Pharm Assoc (Wash). 1999;39(2):146–50.Google Scholar
  36. 36.
    Biondi L, Nairn JG. Stability of 5-fluorouracil and flucytosine in parenteral solutions. CJHP. 1986;39(3):60–4.Google Scholar
  37. 37.
    Roberts S, Sewell GJ. Stability and compatibility of 5-fluorouracil infusions in the Braun Easypump®. J Oncol Pharm Pract. 2003;9:109–12. doi: 10.1191/1078155203jp109oa.CrossRefGoogle Scholar
  38. 38.
    Dine T, Khalfi F, Gressier B, Luyckx M, Brunet C, Ballester L, et al. Stability study of fotemustine in PVC infusion bags and sets under various conditions using a stability-indicating high-performance liquid chromatographic assay. J Pharm Biomed Anal. 1998;18(3):373–81. doi: 10.1016/S0731-7085(98)00096-X.PubMedCrossRefGoogle Scholar
  39. 39.
    Xu Q, Zhang Y, Trissel LA. Physical and chemical stability of gemcitabine hydrochloride solutions. J Am Pharm Assoc (Wash). 1999;39(4):509–13.Google Scholar
  40. 40.
    Benaji B, Dine T, Goudaliez F, Luyckx M, Brunet C, Mallevais ML, et al. Compatibility study of methotrexate with PVC bags after repackaging into two types of infusion admixtures. Int J Pharm. 1994;105:83–7. doi: 10.1016/0378-5173(94)90239-9.CrossRefGoogle Scholar
  41. 41.
    Lecompte D, Bousselet M, Magnam J. Stability of mitoxantrone (Novantrone®) after dilution in PVC infusions. J Pharm Clin. 1990;9:159–65.Google Scholar
  42. 42.
    André P, Cisternino S, Roy AL, Chiadmi F, Schlatter J, Agranat P, et al. Stability of oxaliplatin in infusion bags containing 5% dextrose injection. Am J Health Syst Pharm. 2007;64(18):1950–54. doi: 10.2146/ajhp060369.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhang Y, Trissel LA. Physical and chemical stability of pemetrexed in infusion solutions. Ann Pharmacother. 2006;40(6):1082–5. doi: 10.1345/aph.1G715.PubMedCrossRefGoogle Scholar
  44. 44.
    Xu QA, Trissel LA, Zhang Y, Martinez JF, Gilbert DL. Stability of thiotepa (lyophilized) in 5% dextrose injection at 4 and 23 degrees C. Am J Health Syst Pharm. 1996;53(22):2728–30.PubMedGoogle Scholar
  45. 45.
    Murray KM, Erkkila D, Gombotz WR, Pankey S. Stability of thiotepa (lyophilized) in 0.9% sodium chloride injection. Am J Health Syst Pharm. 1997;54(22):2588–91.PubMedGoogle Scholar
  46. 46.
    Krämer I, Thiesen J. Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices. J Oncol Pharm Pract. 1999;5(2):75–82.Google Scholar
  47. 47.
    Dine T, Luyckx M, Carter JM, Brunet C, Cazin M, Goudaliez F, et al. Stability and compatibility studies of vinblastine, vincristine, vindesine and vinorelbine with PVC infusion bags. Int J Pharm. 1991;77:279–85. doi: 10.1016/0378-5173(91)90328-L.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Frédéric Benizri
    • 1
    Email author
  • Brigitte Bonan
    • 2
  • Anne-Laure Ferrio
    • 2
  • Marie-Laure Brandely
    • 3
  • Vincent Castagné
    • 4
  • Nathalie Théou-Anton
    • 5
  • Muriel Verlinde-Carvalho
    • 6
  • Laurent Havard
    • 2
  1. 1.PharmacyHospital at Home, AP-HPParisFrance
  2. 2.PharmacyGeorges Pompidou European Hospital, AP-HPParisFrance
  3. 3.PharmacyHôtel-Dieu Hospital, AP-HPParisFrance
  4. 4.PharmacyPaul Brousse Hospital, AP-HPParisFrance
  5. 5.PharmacyBeaujon Hospital, AP-HPParisFrance
  6. 6.PharmacyHenri Mondor Hospital, AP-HPParisFrance

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