THE PRESCRIPTION OF ANTHRACYCLINES DURING PREGNANCY IN HAEMATOLOGY: CASE REPORTS AND LITERATURE REVIEW

C Peloso, MT Baylatry, E Elefant, F Isnard, C Fernandez, AC Joly.

Saint-Antoine Hospital (APHP), Pharmacy, Paris, France; Trousseau Hospital (APHP), Crat, Paris,
France; Saint-Antoine Hospital (APHP), Haematology, Paris, France

Background Anthracyclines are one of the most important groups of drugs used nowadays in cancer chemotherapy. Chemotherapy is essential in the management of haematological malignancies (HM). When acute leukaemia (AL), aggressive non-Hodgkin’s lymphoma (NHL) or Hodgkin’s lymphoma (HL) occur during pregnancy, chemotherapy is an emergency but foetal risk must be considered.

Purpose To evaluate foetal and maternal outcomes associated with the prescription of anthracyclines in pregnant women with HM.

Materials and Methods Cases of pregnant women with AL, NHL or HL treated by anthracyclines were collected from the Teratogenic Agent Information Centre (TAIC), a French reference centre providing specialised information for clinicians about drug use in pregnancy. A literature review was performed in the PubMed and Embase databases until May 2012 (keywords: pregnancy, acute leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, cancer chemotherapy, doxorubicin, daunorubicin and idarubicin). Selection criteria of articles: diagnosis of HM and anthracycline prescription during pregnancy, foetal outcome.

Results We report 5 cases of pregnant women with HM (4 AL, 1 HL) treated early in the 3rd trimester by chemotherapy with doxorubicin or daunorubicin at standard dosage. All 5 newborns were normal, but 2 were premature deliveries. 3 maternal outcomes were complete remission (2 unknown). 81 articles were selected, corresponding to 134 pregnant women with AL (95 cases), HL (16) or NHL (23) treated by chemotherapy with daunorubicin (65 cases), doxorubicin (59) or idarubicin (10). Normal neonatal outcomes (100/134) were 88%, 68% and 40% for doxorubicin, daunorubicin and idarubicin respectively, 79%, 77% and 45% for exposure from 3rd (26 cases), 2nd (69) and 1st trimester (11) respectively and 96%, 81% and 68% in NHL, LH and AL respectively. Foetal toxicities were death (20), growth retardation (8) and congenital abnormalities (6). Only idarubicin was associated with foetal cardiomyopathy. 97 maternal outcomes were known with remissions (71 cases) and progressions, relapses or deaths (26 cases).

Conclusions Embryo-foetal toxicity depends on gestational age, anthracycline and HM. 2nd or 3rd trimester exposures were mainly associated with favourable neonatal outcomes. Idarubicin was specifically associated with a risk of foetal cardiotoxicity, probably due to its lipophilic nature, facilitating placental transfer. Unfavourable foetal outcomes were more frequent in AL compared to lymphomas, probably refl ecting that chemotherapy can never be delayed till post-partum in AL. It is possible to prescribe anthracyclines for HM in the 2nd and 3rd trimesters of pregnancy with minimal risk to the developing foetus but then the treatment must be conducted by a multidisciplinary team.

Reference Eur J Hosp Pharm 2013;20(Suppl 1):A1–238

TRABECTEDIN FOR METASTATIC SOFT TISSUE SARCOMA – A RETROSPECTIVE ANALYSIS

AR Gaspar, PF Tavares, J Casanova. Centro Hospitalar e Universitário de Coimbra, UTAL – Bone and Soft Tissue Sarcoma Unit, Coimbra, Portugal

Background: soft tissue sarcomas (STSs) are rare tumours arising from connective tissues characterised by high morphologic and biologic heterogeneity, as well as by limited responsiveness to cytotoxic chemotherapeutic agents. Trabectedin was approved in 2007 for patients with advanced STS after failure of anthracyclines and ifosfamide, or for patients unsuited to receive these agents.

Purpose: to obtain basic epidemiological information on patients with soft tissue sarcomas, standard treatment procedures and results of trabectedin treatment in clinical practise.

Materials and methods: this retrospective study analysed 31 STS patients treated with trabectedin between January 2009 and September 2012. A retrospective cohort study of all patients with a diagnosis of STS treated with trabectedin 1.5 mg/m2, D1, 24 hours’ continuous IV infusion, every 3 weeks. Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE). Progression-free survival curves (PFS) and Overall Survival (a 95% confi dence interval was used) were estimated by using the Kaplan-Meier method.

Results: median age at the initiation of trabectedin therapy was 52 years (18–79 years). Leiomyosarcoma was the most frequent tumour (25.8%) and liposarcoma occurred in 16.2% of the patients. Median number of cycles administered was 6.7 (2–16 cycles). Thrombocytopenia, leukopenia (16.1% of patients), asthenia (12.9%) and elevation of liver transaminases (9.7% of patients) were the most frequent adverse effects. Nine patients achieved a partial remission (PR) and in 3 the disease stabilised (SD). Median overall survival (95% CI) was 6.0 months (0.8; 36.1), median progression-free survival (PFS) (95% CI) was 11.48 months. PFS for all patients was 90.3% at three months and 79.0% at six months.

Conclusions: our results indicate that trabectedin shows promise as an effective and tolerable new drug for the treatment of patients with STS.

No conflict of interest.

Eur J Hosp Pharm 2013;20(Suppl 1):A1–238

IPILIMUMAB FOR ADVANCED MELANOMA: DRUG USE REVIEW

AR Rubio Salvador, J Medina Martínez, JM Martínez Sesmero, P Moya Gómez, MA Cruz Mora, JI Chacón López-Muñiz, JJ Cía Lecumberri.

Hospital Virgen de la Salud, Pharmacy, Toledo, Spain; Hospital Virgen de la Salud, Oncology, Toledo, Spain

Background: ipilimumab is a recombinant, fully human monoclonal antibody (IgG1) which blocks the inhibitory effects of cytotoxic T-lymphocyte antigen 4 (CTLA4), a negative regulator of T-cell activation. It has been approved for the treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic treatment for advanced disease.

Purpose: to review the effectiveness and safety profi le of ipilimumab in the treatment of adult patients with advanced melanoma.

Materials and methods: medical record review and retrospective analysis (January 2011 to September 2012) of prescriptions recorded in the Integral Oncology Patient Information System (ONCOBASS) in a teaching general hospital. Previous drug use, dose, line of chemotherapy, number of cycles administered, objective response rate and toxicity were analysed.

Results: a total of 5 patients with metastatic melanoma were prescribed ipilimumab (2 male, 3 female), median age 45 (36–60). The 4 cycles of treatment planned were completed by 3 patients, 1 continues in active treatment at the moment of fi nishing this study and the other one has been lost to follow-up due to change of hospital. In the group of four patients who received treatment, 2 were prescribed ipilimumab as a second line after failure of a temozolomide- based regimen, and 2 were prescribed ipilimumab as third line after two regimens based on immunotherapy, temozolomide or vemurafenib. After completing the 4 cycles planned, 1 patient maintained complete response (16 months) and 1 patient showed stable disease (maintained for 5 months), and the other one is in evaluation. No patients suffered grade 3–4 toxicity and the treatment was well tolerated.

Conclusions: ipilimumab has shown effectiveness and safety in the treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic treatment for advanced disease in our patients, although data from more patients and longer-term studies are required.

No confl ict of interest.

Eur J Hosp Pharm 2013;20(Suppl 1):A1–238

Vidarabina pomada

Vidarabina............................................................................3 g 
Vaselina Sólida Branca q.s.p............................................100 g

Este produto deve ser preparado em área classificada, seguindo protocolo para reconstituição de soluções de drogas citostáticas. Misturar os componentes da formulação até aspecto homogêneo. Estocado em pote de vidro e plástico âmbar na concentração de 3%. Estabilidade de 21 dias em temperatura ambiente.

Referência bibliográfica: Trissel LA. Trissel’s Stability of Compounded Formulations, 2^nd ed. Washington, DC: American Pharmaceutical Association; 2000.

Vinorelbina: estabilidade após diluição

Forma Preparada:  solução injetável

A Partir de:  solução injetável

Nome Comercial:  Navelbine® (Asta Medica)

Concentração:  0,5 mg/mL; 2 mgmL

Estabilidade:  5 dias em bolsa plástica de PVC para infusão via endovenosa

  

Modo de Preparo: Calcular a quantidade requerida de cada componente da formulação para o total de material a ser preparado. Este produto deve ser preparado em sala limpa, por um profissional qualificado em manipulação asséptica. Sala limpa: área com controle ambiental definido em termos de contaminação por partículas e microbiana, projetada e utilizada de forma a reduzir a introdução, a geração e a retenção de contaminantes em seu interior. Na capela de fluxo laminar, misturar assepticamente os componentes da manipulação, seguindo protocolo para reconstituição de soluções de drogas citostáticas. Diluída em soro fisiológico 0,9% ou soro glicosado 5%.

Estocagem:  TEMPERATURA AMBIENTE

Etiqueta:  Para Uso Injetável e Proteger da Luz

Referência da Estabilidade:

1. Lieu CL, Chin A, Gill MA. Five-day Stability of Vinorelbine in 5% Dextrose and in 0,9% Sodium Chloride Injection at Room Temperature. IJPC 1999;3(1):67-8

Livro de Oncohematologia: Manual de Diluição de Medicamentos Citostáticos

ONCOHEMATOLOGIA. Manual de Estabilidade, Diluição e Reconstituição de Medicamentos Citostáticos, 1ª edição pic.twitter.com/UtcmFH27pY
— Gilberto B. Souza (@gilbertobarcelo) November 19, 2013

Livro Manual de Drogas Injetáveis, 3ª edição

Manual de Drogas Injetáveis, 3ª edição. Atualizado com tabelas mL/hora ou mcg/kg/min para diversos medicamentos. pic.twitter.com/JY8biI80aN
— Gilberto B. Souza (@gilbertobarcelo) November 18, 2013