melphalan and Neoplasms--Germ-Cell-and-Embryonal

Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients.. This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays.. At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria.. We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches.

Topics: Cytokines; Disease Progression; Disease-Free Survival; Humans; Immunoglobulin G; Male; Melphalan; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal; Organoplatinum Compounds; Prognosis; Prospective Studies; Testicular Neoplasms; Translational Research, Biomedical

The present study evaluated the feasibility and effectiveness of myeloablative high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors (CNS-GCTs). Eleven patients with non-germinomatous germ cell tumors and nine patients with germinomas were enrolled. Patients received between two and eight cycles of conventional chemotherapy prior to HDCT/autoSCT with or without radiotherapy. Overall, 16 patients proceeded to the first HDCT/autoSCT, and nine proceeded to the second HDCT/autoSCT. CTE (carboplatin-thiotepa-etoposide) and cyclophosphamide-melphalan (CM) regimens were used for the first and second HDCT, respectively. Toxicities during HDCT/autoSCT were acceptable, and there were no treatment-related deaths. Twelve patients experienced relapse or progression; however, four patients with germinomas remain alive after subsequent RT. Therefore, a total of 12 patients (four NGGCTs and eight germinomas) remain alive with a median follow-up of 47 months (range 22-90) after relapse or progression. The probability of 3-year overall survival was 59.1 ± 11.2 % (36.4 ± 14.5 % for NGGCTs vs. 88.9 ± 10.5 % for germinomas, P = 0.028). RT, particularly craniospinal RT, was associated with a better tumor response prior to HDCT/autoSCT and a better final outcome. In conclusion, HDCT/autoSCT was feasible, and survival rates were encouraging. Further study with a larger cohort of patients is needed to elucidate the role of HDCT/autoSCT in the treatment of relapsed or progressed CNS-GCTs.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Central Nervous System Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Etoposide; Feasibility Studies; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Myeloid Cells; Neoplasm Recurrence, Local; Neoplasms, Germ Cell and Embryonal; Prognosis; Prospective Studies; Salvage Therapy; Survival Rate; Thiotepa; Transplantation, Autologous; Young Adult

Topics: Antineoplastic Agents, Alkylating; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Myeloablative Agonists; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neuroblastoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

As the dose-limiting toxicity of mitoxantrone is hematological, the drug is suitable for dose escalation and use in intensive chemotherapy followed by autologous bone marrow rescue. Adult patients with therapy-resistant solid tumors received a regimen of high-dose cyclophosphamide (7 g/m2) and escalating doses of mitoxantrone in dose steps of 30, 45, 60, and 75 mg/m2. Both drugs were given i.v. on 3 consecutive days. Despite the addition of mesnum (3.5 to 7 g/m2), hemorrhagic cystitis occurred on the second day in four of eight patients, irrespective of the mesnum or mitoxantrone dose. Therefore, the cyclophosphamide in the combination regimen was replaced by high-dose melphalan (180 mg/m2). Mucositis was dose limiting at 75 mg/m2 of mitoxantrone. Responses were seen in eight of ten evaluable patients with four complete responses. Three responders received, after the autologous bone marrow transplantation program, radiotherapy or surgery on pretreatment bulky tumor localizations. Five patients still have disease-free survival after 9 to 36 mo. Pharmacokinetic studies of mitoxantrone were performed by high-performance liquid chromatography with UV detection. The plasma disappearance of mitoxantrone fitted into a three-compartment model with a mean t1/2 alpha of 10 min, a mean t1/2 beta of 96 min, and a slow elimination phase of 172 h. The mean distribution volume was 4294 +/- 3836 liters. We conclude that the high-dose cyclophosphamide-mitoxantrone regimen led to unexpected bladder toxicity, but the combination of melphalan (180 mg/m2) and mitoxantrone (60 mg/m2) can probably be given without major extramedullary toxicity. However, more patients should be evaluated at this dose before definite conclusions can be drawn about toxicity.

Topics: Adult; Bone Marrow Transplantation; Breast Neoplasms; Cyclophosphamide; Female; Humans; Male; Melphalan; Middle Aged; Mitoxantrone; Neoplasms; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Stomach Neoplasms

A case of primary malignant mixed mesodermal tumor (MMMT) of the ovary arising de novo in a post-menopausal multiparous female is reported. The tumor contained heterologous elements in the form of cartilage and fat in addition to carcinosarcomatous areas. Post-operatively, single-agent chemotherapy was administered and up to the time of reporting the patient has been alive and well. Because of the rarity of these tumors the proper treatment remains a dilemma. The differential diagnosis of MMMT of ovary and teratocarcinoma is considered, as the two are confused frequently.

Topics: Carcinosarcoma; Diagnosis, Differential; Female; Humans; Melphalan; Middle Aged; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Teratoma

Sixty-eight patients with "advanced ovarian carcinoma" were entered into an ongoing phase-II trial for remission induction with cis-platinum (DDP) 80 mg/m2 i.v. on day 1 followed by forced saline diuresis, melphalan (L-PAM) 12 mg/m2 i.v. on day 2 and hexamethylmelamine (HMM) 130 mg/m2 p.o. X 14 days from days 8-21 in six monthly cycles following operative resection and/or staging. Fifty-one patients were evaluable for response, ten had not completed six courses and could not be assessed, two patients died early (one probably of toxicity), and five patients refused treatment and follow-up. Thirty-Two patients had serous, endometrioid or undifferentiated carcinomas of the ovary. Of these, 11 (35%) achieved a pathologically proven complete remission (CR), five (16%) were NED after second-look (residual disease in ovary or removed omentum with all other biopsies and cytology washings negative), eight (32%) achieved a partial remission (PR), and three (12%) had progressive disease. None of the seven patients with clear-cell carcinoma and none of the three patients with Mullerian tumor of the ovary responded. Six of nine patients with tumors of uncertain origin or proven metastasis to ovary did not respond to treatment. These preliminary results indicate that advanced ovarian carcinomas form a heterogeneous group of recognizable neoplastic diseases with striking variation in response to treatment.

Topics: Adenocarcinoma; Altretamine; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Evaluation; Female; Humans; Melphalan; Middle Aged; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Prognosis; Reoperation

Topics: Choriocarcinoma; Cyclophosphamide; Dysgerminoma; Female; Humans; Male; Melphalan; Methotrexate; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pregnancy; Teratoma; Testicular Neoplasms; Vincristine

Topics: Humans; Male; Melphalan; Neoplasm Metastasis; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms, Second Primary; Testicular Neoplasms

Topics: Drug Therapy; Dysgerminoma; Female; Humans; Male; Melphalan; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Seminoma; Testicular Neoplasms

Topics: Dysgerminoma; Female; Humans; Male; Melphalan; Neoplasms; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Phenylalanine; Seminoma; Testicular Neoplasms; Testis