1/5. The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid.BACKGROUND: The development of metastatic disease throughout the neuroaxis from primary central nervous system (CNS) tumors and non-CNS tumors suggests the cerebrospinal fluid (CSF) is an important source of exposure for chemotherapeutic agents. In non-human primates, a 4-hour, as compared to a 30-minute, topotecan (TPT) infusion prolonged TPT exposure in the CSF. PATIENT AND methods: We evaluated this approach in a 51-year-old woman with breast cancer metastatic to the CNS. TPT was administered at 1.5 mg/m2/day (cycle 1) and 1.0 mg/m2/day (cycles 2 and 3) as a 30-minute infusion on days 0-4, and as a 4-hour infusion on day 5. Cycles were repeated every 21 days. plasma, lateral ventricular CSF, and lumbar CSF samples were obtained after 30-minute and 4-hour infusions, and assayed for TPT lactone and total by HPLC. A three-compartment model was used to calculate area under the plasma (AUCplasma) and lateral ventricular CSF (AUCCSF) concentation-time curves. TPT CSF penetration was calculated as the ratio of AUCCSF to AUCplasma. RESULTS: Mean /- SD values for TPT total CSF penetration in lateral CSF after 30-minute and 4-hour infusions were 0.25 /- 0.15 and 0.29 /- 0.02, respectively. TPT total lumbar CSF concentration was 3-fold greater after a 4-hour as compared to a 30-minute infusion. For TPT lactone and TPT total, time > 1 ng/ml in lateral CSF was 1.8- and 1.7-fold greater, respectively, for a 4-hour as compared to a 30-minute infusion. CONCLUSIONS: Prolonging TPT infusion from 30 minute to 4 hours increases the duration of exposure in the CSF. This study demonstrates the ability to develop treatment strategies of systemically administered chemotherapy to enhance cytotoxic exposure in the CSF.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/5. Delayed surgical resection of central nervous system germ cell tumors.OBJECTIVE: To determine the value of delayed surgical resection in patients with central nervous system germ cell tumors who exhibit less than complete radiographic response despite declining serum and cerebrospinal fluid (CSF) tumor markers after initial chemotherapy. methods: We retrospectively analyzed 126 patients enrolled on two international multicenter clinical trials (the First and Second International central nervous system Germ Cell Tumor Studies) for patients with newly diagnosed central nervous system germ cell tumors. After at least three cycles of chemotherapy, 10 of these patients underwent delayed surgical resection owing to evidence of residual radiographic abnormalities despite declining or completely normalized serum and CSF levels of alpha-fetoprotein and human chorionic gonadotropin. RESULTS: Eight of these patients demonstrated nongerminomatous germ cell tumor elements at the time of initial diagnosis. In these patients, either serum or CSF tumor markers were elevated initially. Two patients demonstrated pure germinomas with normal levels of serum and CSF tumor markers. After chemotherapy, radiographic evaluation revealed a partial response in seven patients, a minor response in one patient, and stable disease in two patients. All 10 patients had either normal or decreasing levels of serum and CSF tumor markers before second-look surgery. At delayed surgical resection, 7 of the 10 patients underwent gross total resection, and 3 patients underwent subtotal resection of residual lesions. Pathological findings at second-look surgery demonstrated three patients to have mature teratomas, two with immature teratomas, and five with necrotic or scar tissue alone. To date, 7 of the 10 patients have had no recurrence during an average follow-up time of 36.9 months (range, 3-96 mo). Three of four patients with nongerminomatous germ cell tumors who had tumor markers that were decreased, but not normalized, before second-look surgery eventually developed tumor dissemination/progression, and they required subsequent radiation therapy despite having teratoma or necrosis/scar tissue at delayed surgery. In contrast, three of four patients with nongerminomatous germ cell tumors and completely normalized markers did not progress and did not require radiation therapy. CONCLUSION: Delayed surgical resection should be considered in patients with central nervous system germ cell tumors who have residual radiographic abnormalities and normalized tumor markers, because these lesions are likely to be teratoma or necrosis/scar tissue. However, second-look surgery should be avoided in patients whose tumor markers have not normalized completely.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
3/5. T-cell lymphoblastic lymphoma presenting with a breast mass.Lymphomas secondarily involving the breast are uncommon, although they do represent the largest group of tumors metastatic to breast. A 20-year-old female with lymphoblastic lymphoma (LBL) presented here with 3 month history of weight loss, night sweats, fatigue and a mass in her left breast. Her physical examination revealed a left breast mass, lympadenopathy, bilateral pleural effusion and hepatomegaly. WBC count was 17,710/mm3 and LDH was mildly elevated. breast ultrasound showed a 1.7 cm mass in the inner lower quadrant of left breast. biopsy of the breast mass showed diffuse infiltration with small, round atypical cells which did not stain with CD20, CD43, CD34, cytokeratine and were positive for CD3. She was diagnosed as leukemic phase of a precursor T-cell LBL and treated with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), intrathecal methotrexate and cranial radiotherapy, achieving a complete response. She then was started on maintenance therapy. Four months later she returned with CNS involvement and was started on induction treatment. She had a very aggressive course of disease and died only 12 months after diagnosis. breast involvement is very rarely seen in precursor T-cell LBL/ALL and in this patient occurred secondarily as part of widespread disease.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
4/5. Preliminary individual adjuvant chemotherapy for primary central nervous system lymphomas based on the expression of drug-resistance genes.Individual adjuvant chemotherapy based on the expression of drug-resistance genes by reverse transcription-polymerase chain reaction (RT-PCR) was applied for the treatment of patients with primary central nervous system lymphoma (PCNSL). Three patients were included in this study. The drug-resistance genes were investigated in tumor tissues by RT-PCR with the specific primers for MDR-1, MRP-1, MRP-2, MXR-1, MGMT, GST-pei, and topoisomerase II alpha. We selected proper anticancer agents based on mRNA expression of these drug-resistance genes. In case 1, RT-PCR showed overexpression of MDR-1, MRP-1, MGMT, and topoisomerase II alpha mRNA, whereas neither MRP-2, MXR-1, nor GST-pei was expressed. The patient was given high-dose methotrexate (HD-MTX) for the first cycle of treatment; however, the reduced tumor showed regrowth before the second cycle of treatment, and therefore the patient was given carboplatin, mitoxantrone, and HD-MTX in the second and third cycles. Finally, magnetic resonance (MR) images showed a complete response. The other two cases showed similar patterns of drug-resistance gene expression, such that mRNAs of MRP-2, MXR-1, MGMT, GST-pei, and topoisomerase II alpha were overexpressed, whereas neither MDR-1 nor MRP-1 was expressed. They were successfully treated with combined HD-MTX and CHOP (cyclophosphamide, doxorubicin, vincristine, and predonsone). Our preliminary trial of individual adjuvant chemotherapy based on RT-PCR suggested that it was an effective and beneficial therapy for PCNSL. Although HD-MTX therapy is supposed to be effective for patients with MDR-1-negative PCNSL, MTX alone should be avoided in the choice of the anticancer drug for the treatment of MDR-1-positive PCNSL.- - - - - - - - - - ranking = 1.5keywords = cycle (Clic here for more details about this article) |
5/5. seminoma with isolated central nervous system relapse, and salvage with craniospinal irradiation.We report a case of a patient with isolated central nervous system relapse of classical seminoma, refractory to intrathecal and systemic chemotherapy, but successfully salvaged with craniospinal axis irradiation. A 44-year-old man with bulky Stage II classic seminoma obtained complete remission with four cycles of cisplatin etoposide combination chemotherapy, but relapsed with lumbar vertebral metastases with epidural spinal cord compression 5 months after completion of primary treatment. He underwent laminectomy, local radiotherapy, and salvage chemotherapy. Two months later he developed cranial nerve palsies, and magnetic resonance imaging confirmed leptomeningeal disease. After brain radiotherapy, systemic and intrathecal chemotherapies were begun but tumor recurred around the cauda equina, producing paraparesis. The patient received salvage craniospinal irradiation, with resolution of paraparesis and cranial nerve palsies. Thirty months after completion of craniospinal radiotherapy, he remains in complete remission. We suggest consideration of craniospinal axis irradiation as salvage therapy in patients with isolated central nervous system relapse of seminoma.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |