BACKGROUNDThe primary objective of this study was to determine whether addition of the selective P‐glycoprotein (P‐gp) inhibitor tariquidar (XR9576) to chemotherapy could induce an objective tumor response in patients who previously were resistant to the same agents. The secondary objectives were to evaluate P‐gp expression by immunohistochemistry (IHC), to determine functional activity of the P‐gp transporter before and after administration of tariquidar with serial technetium‐99m (99mTc)‐sestamibi scans, and to correlate those parameters with clinical response.METHODSSeventeen women with Stage III–IV breast carcinoma were included in the study who progressed (n = 13 women) or had stable disease (n = 4 women) on doxorubicin‐containing or taxane‐containing chemotherapy regimens. During the study, the same chemotherapy was continued without dose modifications, but tariquidar (150 mg intravenously) was added to the treatment regimen.RESULTSThirty‐six percent of patients had P‐gp‐positive tumors by IHC, and 5 patients (29%) experienced increases ≥ 10% in sestamibi uptake (median increase, 40%; range, 10–63%) after the administration of tariquidar. There was one partial response in a patient who had the greatest increase in sestamibi uptake and who also showed inducible P‐gp expression. There was one patient who experienced severe doxorubicin/docetaxel‐related toxicity after tariquidar was added to her chemotherapy regimen.CONCLUSIONSTariquidar showed limited clinical activity to restore sensitivity to anthracycline or taxane chemotherapy. Functional imaging of the tumor with 99mTc‐sestamibi scans before and after administration of multidrug‐resistance inhibitor may be useful to identify the small subset of patients who could benefit from multidrug‐resistance modulation in future trials. Cancer 2005. © 2005 American Cancer Society.

Epithelial carcinoma of the ovary is one of the most common gynaecologic malignancies, and the fourth most frequent cause of cancer death in women (Yancik, 1993). The asymptomatic early stages of ovarian cancer mean that most patients have widespread disease at the time of diagnosis. Patients with FIGO stage III and IV disease and significant residual tumour masses after primary surgery can expect a 5-year survival rate of less than 10%, despite multiple courses of platinum-based chemotherapy (Omura et al, 1991).Until the mid-1990s, the combination of a platinum compound and an alkylating agent was considered best therapy for these patients, but a new standard of care emerged after the publication of trial GOG-111 in 1996 which was followed by the first reports of the INTERGROUP trial, OV10, in 1998(Piccart et al, 2000. Both these large, prospective randomized studies demonstrated that patients treated with cisplatin-paclitaxel in combination had significantly higher response rates, progression-free survival and overall survival compared with the previous standard treatment of cisplatin and cyclophosphamide. However, this higher efficacy was at the expense of greater toxicity. In GOG-111, 135 mg/m 2 paclitaxel was administered with 75 mg/m 2 cisplatin as an inconvenient 24-hour infusion, and neurotoxicity in particular was more frequently observed (28% vs 21%, P ≤ 0.05). Reducing the paclitaxel infusion time to 3 hours (with a concomitant increase in dose to 175 mg/m 2 ) in OV.10 produced a further increase in neurotoxicity, with 19.6% patients experiencing CTC grade III or IV sensory neurotoxicity, compared with 1% of patients receiving cisplatin-cyclophosphamide. Meta-analyses incorporating data on nearly 10 000 patients from 45 randomized trials suggested that the substitution of carboplatin for cisplatin was equally effective either as a single agent or in combination (Aabo et al, 1998). The addition of carboplatin to paclitaxel was expected to produce less emesis and neurotoxicity, but greater myelosuppression compared with cisplatin-paclitaxel. Seven phase I-II trials of carboplatin-paclitaxel combinations have been reported, involving 260 chemo-naïve ovarian cancer patients (Bookman et al, 1996;Lhomme et al, 1996;Bolis et al, 1997;duBois et al, 1997;Huizing et al, 1997;ten Bokkel Huinink et al, 1997;Siddiqui et al, 1997). Doses of carboplatin ranged from AUC 5-10, and paclitaxel from 120-250 mg/m 2 and almost all the trials used a 3-hour paclitaxel administration schedule. As expected the major toxicities in all studies were myelosuppression and neurotoxicity, however, an apparent reduction in the expected level of thrombocytopenia was observed in many of these trials, and an interaction at the megakaryocyte level rather than a pharmacokinetic interaction is thought to be responsible (Calvert et al, 1995). Antitumour activity was substantial, with response rates ranging from 70-100%.The direct comparison of carboplatin-paclitaxel with cisplatinpaclitaxel in a prospective, randomized trial as first-line t...

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Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.