ABSTRACT
Chemo-induced thrombocytopenia is a limiting toxicity among patients receiving temozolomide (TMZ) as first-line treatment for glioblastoma. We aimed to compare early platelet concentration kinetics, hematological safety profile, and impact on survival following the initiation of either the brand-name or a generic TMZ formulation. A retrospective trial was conducted in patients suffering from newly diagnosed glioblastoma. Patients were treated with TMZ at 75 mg/m2 per day during six weeks, concomitantly with radiotherapy. Platelet concentration was collected each week. Primary endpoint was to perform a linear mixed-effect model of platelet concentration kinetic over weeks. A total of 147 patients were included as follows: 96 received the brand-name TMZ, and 51 received a generic TMZ formulation. Exposition to the generic was a significant variable that negatively influenced the platelet kinetics in the radiotherapy and concomitant TMZ phase, P = 0.02. Grade ≥3 chemo-induced thrombocytopenia was more frequent in the generic group: 19.6% [95% CI 8.7-30.5%] vs 3.1% [0-6.6%], P = 0.001. Exposition to the generic formulation of TMZ led to increase early treatment discontinuation due to TMZ-induced thrombocytopenia and was a worsening independent prognostic factor on overall survival: adjusted HR 1.83 [1.21-2.8], P = 0.031. These data suggest that exposition to a generic formulation of TMZ vs the brand-name product is associated with higher early platelet decrease leading to clinically relevant impacts on treatment schedule in glioblastoma. Further prospective trials are needed to confirm these results.
Subject(s)
Antineoplastic Agents, Alkylating/adverse effects , Blood Platelets/drug effects , Brain Neoplasms/drug therapy , Drugs, Generic/adverse effects , Glioblastoma/drug therapy , Temozolomide/adverse effects , Thrombocytopenia/chemically induced , Antineoplastic Agents, Alkylating/chemistry , Brain Neoplasms/mortality , Drug Compounding , Drugs, Generic/chemistry , Female , Glioblastoma/mortality , Humans , Kinetics , Male , Middle Aged , Platelet Count , Retrospective Studies , Risk Assessment , Risk Factors , Temozolomide/chemistry , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/mortality , Treatment OutcomeABSTRACT
OBJECTIVES: The study evaluated the stability of three combinations of oxycodone and ketamine diluted in normal saline (NS) after storage for 7â days at 23°C and exposed to light. METHODS: The stability of three mixtures of oxycodone and ketamine (oxycodone 0.4â mg/mL+ketamine 40â mg/mL, oxycodone 10â mg/mL+ketamine 0.1â mg/mL and oxycodone 10â mg/mL+ketamine 40â mg/mL) in NS stored in a polypropylene syringe and a polyvinyl chloride (PVC) bag was studied. The physical characteristics, including pH, colour and precipitation, were evaluated. The samples were analysed in triplicate by a stability-indicating high-performance liquid chromatography method. RESULTS: There was no significant change in the pH values of any solution. No precipitation or change in colour was observed. All formulations maintained more than 95% of the initial concentration of each drug on day 7. No trace of degradation products was detected. CONCLUSIONS: Ketamine (0.1-40â mg/mL) combined with oxycodone (0.4-10â mg/mL) is physically compatible and chemically stable for 7â days when diluted with NS, packaged in polypropylene syringe or PVC bag and stored at 23°C.
ABSTRACT
PURPOSE: Increased expression of αvß3 integrins is involved in tumour angiogenesis. Targeting these receptors with a dedicated peptide containing the RGD sequence may provide information about the receptor status in and around the tumour and about the angiogenesis process involved. The aim of this study was to compare the uptake of [Tc]-HYNIC-RGD in two types of tumours that either express or do not express the αvß3 receptor (NTERA-2 and MDA-MB-231, respectively) and discuss the use of this tracer in experimental models of angiogenesis. PROCEDURES: Uptake of intravenously injected [Tc]-HYNIC-RGD was studied ex vivo and in vivo. Histological analysis of excised tumours was carried out. Percentages of the injected dose uptake per gram of tissue were compared between the two types of tumours and in the periphery and centre of each tumour. RESULTS: [Tc]-HYNIC-RGD was rapidly cleared from blood circulation and excreted through the kidneys. Residual activity was retained in the intestine. Tumour uptake of [Tc]-HYNIC-RGD was high and homogeneous for αvß3-positive cell lines (1.94±0.26%ID/g). Tumour uptake was weak and distributed only in the tumour periphery for αvß3-negative cell lines (0.10±0.02%ID/g, tumour periphery; 0.06±0.01%ID/g, tumour core; P=0.01). These results correlated with vessel distribution. CONCLUSION: Uptake of [Tc]-HYNIC-RGD was more intense in αvß3-positive cell lines than in αvß3-negative cell lines, but tracer distribution was more representative of angiogenic locations in αvß3-negative cell lines. Further clinical and preclinical studies are needed on the use of RGD-related tracers.
Subject(s)
Cell Transformation, Neoplastic , Diagnostic Imaging/methods , Organotechnetium Compounds/pharmacokinetics , Peptides, Cyclic/pharmacokinetics , Animals , Cell Line, Tumor , Humans , Organotechnetium Compounds/chemistry , Peptides, Cyclic/chemistry , Radiochemistry , Rats , Rats, Nude , Teratoma/diagnostic imaging , Teratoma/pathology , Tissue Distribution , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
(Me)FGC(Bz)DEVD was radiolabeled with technetium-99m in high yield. This tracer was preferentially accumulated in apoptotic cells in the in vitro studies. Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors. Therefore, (99m)Tc-(Me)FGCDEVD is a potential tracer for apoptosis detection.
Subject(s)
Apoptosis/physiology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Oligopeptides/chemistry , Radiopharmaceuticals/chemistry , Technetium Compounds/chemistry , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cisplatin/pharmacology , Heterografts , Humans , Isotope Labeling/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Mice , Mice, Nude , Oligopeptides/drug effects , Oligopeptides/pharmacokinetics , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Technetium Compounds/pharmacokineticsABSTRACT
STUDY OBJECTIVES: To develop and validate a self-assessment adherence tool for imatinib in patients with chronic myeloid leukemia (CML), and to correlate the use of this tool with response to treatment and adverse effects. DESIGN: Retrospective cohort study. SETTING: Regional cancer center in France. PATIENTS: Forty-six patients with chronic phase CML treated with imatinib for 6 months or longer as of July 1, 2009. MEASUREMENTS AND MAIN RESULTS: We developed a self-assessment questionnaire consisting of 10 questions to identify patients who were nonadherent to their cancer treatment. Each answer was worth 1 point, resulting in a possible maximum score of 10. The questionnaire was validated in patients receiving imatinib, using an objective adherence evaluation: a patient's score on the self-assessment questionnaire was correlated with prescription refills, expressed as a medication possession ratio. A score of less than 8 was associated with a positive predictive value of 0.83 to have a medication possession ratio below 90%. With use of this questionnaire, half of the patients receiving imatinib would be identified as being nonadherent (sensitivity 0.5). Few adherent patients would be falsely identified as nonadherent, as the questionnaire's specificity was 0.97. CONCLUSION: This self-assessment questionnaire was validated for the first time in patients receiving imatinib for CML treatment. It provides a simple practical tool for health care professionals to assess patient adherence during their routine clinical practice and to propose targeted interventions for those identified as possibly nonadherent.
Subject(s)
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Diagnostic Self Evaluation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Medication Adherence , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/psychology , Male , Medication Adherence/psychology , Middle Aged , Retrospective Studies , Surveys and Questionnaires/standards , Treatment OutcomeABSTRACT
PURPOSE: We assessed whether imaging α(v)ß(3) integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. METHODS: Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles). (18)F-Fluorodeoxyglucose ((18)F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of α(v)ß(3) expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [(99m)Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse α(v)ß(3) expression were performed. RESULTS: Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for (18)F-FDG [mean standardised uptake value (SUV(mean)) = 0.48 ± 0.05] compared to untreated embryonal carcinoma (SUV(mean) = 0.92 ± 0.13) (p = 0.005). α(v)ß(3) imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 ± 1.57) from necrosis (tumour to muscle ratio = 1.3 ± 0.26) (p = 0.0002). Immunohistochemistry studies showed that α(v)ß(3) integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. CONCLUSION: Imaging α(v)ß(3) integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts.