ABSTRACT
In recent years with the development of targeted agents such as bevacizumab, sunitinib, sorafenib, temsirolimus, and everolimus, the treatment of metastatic renal cell carcinoma has changed dramatically. In clinical practice, sunitinib and bevacizumab are reserved for first-line treatment, but despite various guidelines, optimal treatment is still uncertain. We present, for the first time, a case of a good response to second-line bevacizumab and interferon-alpha in a patient who failed classical sunitinib treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Bevacizumab , Carcinoma, Renal Cell/secondary , Female , Humans , Indoles/administration & dosage , Interferon-alpha/administration & dosage , Kidney Neoplasms/pathology , Lung Neoplasms/secondary , Lymphatic Metastasis , Prognosis , Pyrroles/administration & dosage , Salvage Therapy , Sunitinib , Treatment OutcomeABSTRACT
BACKGROUND: There is pre-clinical evidence of synergism between cisplatin (P) and temozolomide (T) due to higher inhibition by T of O6-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system. T and P are active against malignant gliomas while thalidomide (TH) is emerging as an inhibitor of angiogenesis. PATIENTS AND METHODS: Triplets of patients with malignant brain tumors received escalating doses of P, T and TH up to the dose-limiting-toxicity (DLT) and the maximal tolerated dose (MTD). RESULTS: Seventeen patients were enrolled and a total of 74 cycles were delivered. The MTD was P 75 mg/m2 day 1 and T 150 mg/m2 days 1 to 5 every 21 days with a concomitant 200 mg total daily dose of TH. DLT events were G4 thrombocytopenia and febrile neutropenia. CONCLUSION: Concomitant administration of P 75 mg/m2 day 1, T 150 mg/m2 days 1 to 5 every 21 days and concomitant TH at a total daily dose of 150 mg is feasible and safe. Early efficacy data are encouraging and a phase II study is ongoing.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Astrocytoma/drug therapy , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Dacarbazine/analogs & derivatives , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Temozolomide , Thalidomide/administration & dosage , Thalidomide/adverse effectsABSTRACT
To verify their clinical usefulness in diagnosis and early response to therapy of sideropenic anemia, we compared the behavior of the reticulocyte parameter (RET-Y), a raw measure dependent on size and content of the cell, generated by the Sysmex XE 2100, with the mean reticulocyte volume (MCVr) and mean reticulocyte hemoglobin content (CHr) from the Bayer ADVIA 120 in healthy subjects and patients with iron deficiency anemia. Correlations were high (r = 0.88 and r = 0.94, respectively). All parameters varied significantly as early as 48 hours after the start of intravenous iron therapy (mean differences of 17.4% [RET-Y], 4.5% [MCVr], and 9.5% [CHr]). Sudden decreases in those parameters at interruption of therapy indicate the reappearance of sideropenic erythropoiesis. The receiver operating characteristic curve demonstrated a high degree of efficiency in differentiating moderate or severe iron deficiency anemia from the healthy state. The best association between sensitivity and specificity was at a cutoff of channel 1,624 for RET-Y and 104.5 fL for MCVr (negative and positive predictive values, respectively, of 99.6% and 96.5% for RET-Y and 98.7% and 93.3% for MCVr). RET-Y is correlated closely with CHr and is useful for diagnosis and early monitoring after the administration of intravenous iron.
