Special Access Scheme Research Articles

Ensuring the safety of new medications and devices: are naltrexone implants safe?

Naltrexone implants have not been subject to the usual rigorous scrutiny required for new devices in Australia, but are widely used through the Special Access Scheme.

Caspofungin as salvage monotherapy for invasive aspergillosis in patients with haematological malignancies or following allogeneic stem cell transplantation: efficacy and concomitant cyclosporin A

Caspofungin (CAS) has shown efficacy as salvage monotherapy for invasive aspergillosis (IA) in two open label non-comparative trials. The association between hepatotoxicity and concomitant use of CAS and cyclosporin A (CsA) has not been fully elucidated. We report results on CAS efficacy in the first cohort from outside Europe and USA and the interaction between CAS and CsA. We retrospectively reviewed the charts of all patients with haematological malignancies or postallogeneic haematopoietic stem cell transplant (HSCT) who received >/=1 dose of CAS as salvage monotherapy for IA as part of the Australian Special Access Scheme (4/2001-8/2002). Outcomes were assessed at the end of CAS therapy. Favourable response (FR) was defined as >50% clinical and radiological improvement. Risk factors for elevation of liver transaminases (LTs) were examined using multivariate models. 54 patients were included in the analysis with 47 neutropenic at study entry. Proven or probable IA occurred in 11 and refractory IA in 28. An FR occurred in 26 (48.1%) and predictors for a poor response to CAS were allogeneic HSCT, graft vs. host disease and treatment with CAS for <14 days. Concomitant CAS and CsA for >7 days was an independent risk factor for laboratory hepatoxicity. The CAS efficacy results from the Australian cohort confirm those of previous studies. Close monitoring of LTs is necessary on concomitant CAS and CsA but clinically relevant hepatotoxicity is rare.

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian ‘Special Access Scheme’ experience

AbstractBackground: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units.Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m2 or carboplatin AUC = 5 and pemetrexed 500 mg/m2 every 21 days.Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively.Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.

An Australian experience of pemetrexed in malignant mesothelioma (MM)

7285 Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared to cisplatin alone. However there is only limited data available in a teaching hospital setting outside a clinical trial. Pemetrexed has only been available in Australia on a “special access scheme”(SAS) since 2002. We reviewed our experience of patients treated on the SAS at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, ECOG performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression free and overall survival. All patients received vitamin B12 and folate supplementation. Doses were cisplatin 75 mg/m2 or carboplatin AUC=5 and pemetrexed 500mg/m2 every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years. 88% were ECOG 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. 65% had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy whilst 19% had received prior palliative radiation. 71% were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. 23% had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. Median number of cycles was 4 (range 1–13). Response rate was 25%. No toxicity was observed in 20%, grade 3–4 toxicity in 10% (majority nausea/vomiting). Median progression free and overall survival times from starting pemetrexed were 184 days and 298 days respectively. Conclusions: Pemetrexed is safe and effective in a community setting in MM with results comparable to the recent phase III trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly

An Australian experience of pemetrexed in malignant mesothelioma (MM)

7285 Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared to cisplatin alone. However there is only limited data available in a teaching hospital setting outside a clinical trial. Pemetrexed has only been available in Australia on a “special access scheme”(SAS) since 2002. We reviewed our experience of patients treated on the SAS at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, ECOG performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression free and overall survival. All patients received vitamin B12 and folate supplementation. Doses were cisplatin 75 mg/m2 or carboplatin AUC=5 and pemetrexed 500mg/m2 every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years. 88% were ECOG 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. 65% had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy whilst 19% had received prior palliative radiation. 71% were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. 23% had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. Median number of cycles was 4 (range 1–13). Response rate was 25%. No toxicity was observed in 20%, grade 3–4 toxicity in 10% (majority nausea/vomiting). Median progression free and overall survival times from starting pemetrexed were 184 days and 298 days respectively. Conclusions: Pemetrexed is safe and effective in a community setting in MM with results comparable to the recent phase III trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly

SHPA Standards of Practice for Pharmacy Investigational Drugs Services The Society of Hospital Pharmacists of Australia Committee of Specialty Practice in Investigational Drugs

These standards have been developed for pharmacists involved with investigational drugs in their institutions and replace the previously published ‘SHPA Policy Guidelines for Investigational Drugs’.1 This document deals with investigational drugs used in clinical trials and under the Special Access Scheme (SAS).2 Hospitals and other healthcare agencies are the major centres for clinical studies with investigational drugs and pharmacists in these institutions should be involved with policies and procedures for the safe and ethical use of these drugs.

An appraisal of the clinical use of lamotrigine under the special access scheme

This paper studied the use and efficacy of lamotrigine (LTG), one of the newly developed antiepileptic medications (AEM), released via the Special Access Scheme (SAS). It is argued that the SAS application more closely resembles clinical practice and removes the rigours of clinical drug trialing which of themselves may impose confounding variables into the interpretation of AEM efficacy. Global score evaluation was used to assess efficacy, with scores greater than 4 indicating improvement. Thirty-two patients were administered SAS-LTG, of whom 30 were assessable with a mean duration of therapy of 90 weeks. Twenty-eight (93.3%) patients were assessed at 6 months; 22 (73.3%) patients were assessed at 12 months. Patients with generalised epilepsies received lower doses of LTG than those with partial seizures although this may reflect the use of concomitant sodium valproate (VPA) which is known to increase LTG half life. LTG produced statistically greater global scores in patients with generalised epilepsies (mean 5.6 at 6 months) than for those with partial seizures (mean 4.7 at 6 months). Plasma levels of LTG did not contribute greatly to clinical management. It was concluded that LTG is a relatively safe and effective AEM for certain patients with epilepsy who have proven refractory to the older AEMs. Four patients with refractory generalised seizures were rendered seizure free with the addition of LTG.