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

Background: 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.     

Correction of juvenile hallux valgus deformity associated with metatarsus primus adductus using epiphysiodesis technique

A 4.5-year follow-up retrospective study on the use of epiphysiodesis procedure for juvenile hallux valgus deformity and metatarsus primus adductus deformity shows a good reduction of deformity in nine patients with minimal change in one patient that can be explained due to the timing of the procedure. This is a minor operation for juvenile bunion deformities, using epiphyseal arrest techniques. The only complication to this procedure was one case with a noted metatarsus primus elevatus due to incomplete epiphyseal arrest from dorsal to plantar. This procedure has been found to be a safe and effective way of dealing with juvenile hallux valgus deformity when metatarsus primus adductus is the deforming force. It should be stated that in all cases a follow-up biomechanical examination and casting for orthotics took place and to date no complications, other than what has been previously mentioned, has occurred. I shall continue to perform this procedure where indicated and shall report my findings as they become available.     

Complement levels before and after dives with a high risk of DCS.

BACKGROUND: Previously, complement activation has been associated with decompression sickness (DCS). However data, both in humans and in animals, are controversial. Hypothesis: Complement activation and depletion occurs after exposure to the hyperbaric environment and is associated with increasing risk of DCS. METHODS: We obtained serological samples from 102 dives (120-300 feet of seawater) with a constant partial pressure of O2 set at 1.3 ATA in thirty-five U.S. Navy diver volunteers. Blood was obtained within one hour of diving and within one hour of surfacing. Plasma was extracted and analyzed for complement depletion. The risk of DCS was estimated using a validated model of DCS risk. RESULTS: Pre-post dive concentrations of C3a were significantly related to estimated risk of DCS (Figure 1), but the variation in predicted DCS explained by C3a was small (correlation co-efficient (r2 = 0.19, p < 0.0001). CONCLUSIONS: There was a reduction in total Ca3 levels in divers after exposure to dives with a high estimated risk of DCS. This decomplementation appeared to increase as the estimated risk of DCS increased.     

Peripheral Blood Lymphocyte Surface Antigen Expression and Prognosis in Myeloma: Australian Leukaemia Study Group Study

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (βM) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of β2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator. We conclude that phenotypic analysis of peripheral blood lymphocytes for CD38 antigen at diagnosis may be useful as a prognostic indicator in patients with myeloma.