ABSTRACT
INTRODUCTION: In order to better understand the impact of high-dose on the pharmacokinetics and metabolism of cyclophosphamide, a pharmacological study was performed in children with malignant mesenchymal tumours with metastatic disease. METHODS: Patients received four courses of chemotherapy including two courses of cyclophosphamide. Plasma concentrations of cyclophosphamide and the metabolites 4-ketocyclophosphamide, dechloroethylcyclophosphamide and carboxyphosphamide were determined on days 1, 2 and 3 of each course. A population pharmacokinetic model for cyclophosphamide was developed using non-linear mixed effects modelling and metabolite AUC values were compared between days and courses. RESULTS: Data were available on 21 cyclophosphamide courses from 15 patients. A one compartment model, incorporating a term in surface area for both CL and V, best described cyclophosphamide pharmacokinetics. Typical CL and V on day 1 of treatment for a patient with a SA of 1.4m(2) were 4.3 L/h and 28.5L, respectively. On days 2 and 3 CL increased by 88% (95% CI, 72-105%) and 125% (95% CI, 108-145%) over day 1 levels; V increased by 14% (95% CI, 5-23%) on days 2 and 3. V tended to be larger for males than similarly sized females but no effect of age was found upon CL or V. Significant increases in metabolite AUCs were observed on days 2 and 3 compared to day 1 and a significant increase in CXCP AUC from course 1 to course 3. CONCLUSION: Administration of high-dose cyclophosphamide over several days results in an increase in metabolism, possibly by induction of the activation pathway. This induction is effectively reversed following a four week period between cyclophosphamide doses. The degree of intersubject variation in cyclophosphamide elimination is largely accounted for by body surface area and is less than previously reported.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacokinetics , Cyclophosphamide/pharmacokinetics , Mesenchymoma/drug therapy , Sarcoma/drug therapy , Adolescent , Adult , Antineoplastic Agents, Alkylating/blood , Area Under Curve , Child , Child, Preschool , Cyclophosphamide/analogs & derivatives , Cyclophosphamide/blood , Drug Administration Schedule , Female , Humans , Male , Phosphoramide Mustards/blood , Rhabdomyosarcoma/drug therapy , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: Results are presented of the SIOP study MMT-98 for paediatric metastatic rhabdomyosarcoma (RMS), which evaluated intensive chemotherapy followed by low intensity 'maintenance' chemotherapy in standard risk patients (SRG). For poor risk patients (PRG), the value of a therapeutic window study, sequential high dose monotherapy to achieve a complete response (CR) followed by low dose maintenance chemotherapy was examined. PATIENTS AND METHODS: From November 1998 to 2005, 146 patients aged 6 months to 18 years with metastatic RMS were entered. Forty-five were SRG, i.e. age<10 years and no bone marrow or bone involvement. Treatment was a 6-drug regimen with local therapy of surgery and/or radiotherapy followed by maintenance of 9 courses of vincristine, actinomycin D and cyclophosphamide (VAC). One hundred and one patients were PRG, i.e. >10 years, or with bone marrow or bone metastases. An upfront window study, high dose monotherapy, local treatment and then VAC maintenance therapy were given. RESULTS: With a median follow-up of 1.52 years, the 3-year event-free survival (EFS) and overall survival (OS) for SRG were 54.92% and 62.14%, respectively, whilst for the PRG 16.17% and 23.17%. The corresponding adverse hazard ratio (HR) for the PRG was HR=2.65 (95% CI 1.63-4.31, p-value<0.001) for EFS and HR=2.51 (CI 1.53-4.11, p-value<0.001) for OS. CONCLUSION: SRG patients' EFS and OS were comparable to those of previous studies. For PRG patients there was no improvement in survival.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rhabdomyosarcoma/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Combined Modality Therapy/methods , Cyclophosphamide/administration & dosage , Dactinomycin/administration & dosage , Disease-Free Survival , Female , Humans , Infant , Male , Rhabdomyosarcoma/radiotherapy , Rhabdomyosarcoma/secondary , Rhabdomyosarcoma/surgery , Treatment Outcome , Vincristine/administration & dosageABSTRACT
Typically, adolescence is marked by cognitive and physical developments impacting on self-esteem, independence and sexual awareness, often resulting in increased appearance awareness and dissatisfaction. Adolescents with cancer have the additional burden of illness, treatments and resultant appearance changes. This study aimed to explore the impact of these changes on adolescents who have had cancer. In depth, semi-structured interviews were conducted with six females between 14 and 19 years who had completed treatment within the previous two years, and analysed using Interpretative Phenomenological Analysis (IPA). Concerns around an altered appearance were significant during treatment, serving as a constant reminder of 'difference' and a marker of illness. However, since treatment, participants expressed an apparent shift in views and expectations of their appearance, as well as the value placed on it -- expressing increased satisfaction with their own appearance and a decrease in its importance. While important to acknowledge the distress and challenges experienced by participants, results highlight the need for research and care to focus on positive experiences of patients, rather than simply maladjustment. Explanations for the findings are explored, including the temporary nature of many appearance changes and the life-threatening nature of cancer.
Subject(s)
Adaptation, Psychological , Body Image , Neoplasms/psychology , Psychology, Adolescent , Self Concept , Adolescent , Adult , Female , Humans , Interpersonal Relations , Social ValuesABSTRACT
Gastric teratoma is an extremely rare embryonic neoplasm containing tissue from all three germ layers (ectoderm, endoderm, and mesoderm). A 25-day-old infant presented with anemia and a palpable abdominal mass. Computed tomography (CT) scanning showed a solid and cystic multiloculated tumor of mixed echogenicity and calcifications. An encapsulated bleeding tumor localized to the posterior wall of the stomach with extension to a bowel segment was promptly excised. Histology revealed a grade III immature teratoma with small foci of neuroblastoma. To the best of our knowledge, this is the first infant with gastric teratoma containing foci of neuroblastoma causing bleeding and anemia as presentation symptoms at neonatal age.
Subject(s)
Anemia/etiology , Neuroblastoma/diagnosis , Stomach Neoplasms/diagnosis , Teratoma/diagnosis , Diagnosis, Differential , Gastrointestinal Hemorrhage/etiology , Humans , Infant, Newborn , Male , Neuroblastoma/complications , Neuroblastoma/diagnostic imaging , Neuroblastoma/surgery , Stomach Neoplasms/complications , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Teratoma/complications , Teratoma/diagnostic imaging , Teratoma/surgery , Tomography, X-Ray ComputedABSTRACT
The impact of transfusion of leucodepleted platelet concentrates (PCs) on cytomegalovirus (CMV) disease was assessed in 215 allogeneic (145 unrelated and 70 related donor) transplants over 3 years. In 43%, both donor and patient were CMV seronegative (CMV-/-). All received CMV-seronegative red cells and random leucodepleted PCs. No CMV disease occurred in any CMV-/- (low risk) transplant. CMV infection occurred in 31 seropositive patients (26%); 13 died and five deaths were attributable to CMV disease. When compared with historical controls, who received CMV-seronegative PCs, we found no difference in transfusion-acquired CMV in the current cohort.
