melphalan and Testicular-Neoplasms

The available evidence suggests that if benefit is to be obtained from high dose chemotherapy regimens, it will be in patients whose tumours are either untreated or still responding to conventional therapy. In each of the diseases discussed in this chapter the optimum timing of the treatment regimen has still to be determined. Effective regimens have been found but it is probable that further improvements can be made. In small cell lung cancer initial high dose therapy followed by non-cross-resistant regimens may prove effective. In glioma studies with high dose therapy before irradiation are awaited and may offer the best means of exploiting this approach to treatment. In breast cancer some impressive responses have occurred but the category of patient likely to benefit has not yet been defined. In melanoma high dose treatment is likely to benefit only those patients with probable minimal disease after surgery.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Breast Neoplasms; Carcinoma, Small Cell; Carmustine; Cell Separation; Cisplatin; Colonic Neoplasms; Cyclophosphamide; Etoposide; Glioma; Humans; Lung Neoplasms; Male; Melanoma; Melphalan; Neoplasms; Testicular Neoplasms; Whole-Body Irradiation

Topics: Alkylating Agents; Busulfan; Carcinoma, Bronchogenic; Carmustine; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Mechlorethamine; Melphalan; Neoplasms; Ovarian Neoplasms; Testicular Neoplasms

Topics: Adult; Aging; Castration; Chlorambucil; Cryptorchidism; Cyclophosphamide; Dysgerminoma; Humans; Male; Melphalan; Middle Aged; Mumps; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Testicular Neoplasms; Testis

Topics: Adult; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Child; Cyclophosphamide; Doxorubicin; Drug Combinations; Drug Therapy, Combination; Female; Fluorouracil; Humans; Immunotherapy; Leucovorin; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Prednisone; Rhabdomyosarcoma; Testicular Neoplasms; Thiotepa; Vinblastine; Vincristine

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean +/- SE) of disease-free survival (DFS) at 7 years was 59.5 +/- 9% (95% confidence interval). The estimated chance of relapse was 22.5 +/- 15% with a median follow-up of 88.5 months (range 51-132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD. site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 +/- 12.6%, 37.5 +/- 19.8% and 774 +/- 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3-4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Central Nervous System Neoplasms; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Female; Graft vs Host Disease; Humans; Male; Melphalan; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Recurrence; Testicular Neoplasms; Transplantation, Homologous; Whole-Body Irradiation

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

A 34-year-old man was diagnosed as having solitary testicular plasmacytoma. He had received palliative radiotherapy, several combined chemotherapies including CHOP chemotherapy (vincristine, cyclophosphamide, Adriamycin, and prednisone), MP (melphalan and prednisone) and M-2 protocol (melphalan, prednisone, vincristine, carmustine, and cyclophosphamide), and interferon therapy as 3 million units subcutaneous injection three times a week for 1 year. Extensive bone plasmacytoma developed 7 years later without bone marrow involvement. We suggest that early use of combined chemoradiotherapy and high-dose chemotherapy with autologous stem cell support should be investigated in patients with testicular plasmacytoma with dissemination.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Male; Melphalan; Plasma Cells; Plasmacytoma; Prednisone; Skull Neoplasms; Testicular Neoplasms; Tomography, X-Ray Computed; Vincristine

Telomere stabilisation is a critical step in tumorigenesis and telomerase, an enzyme which counteracts telomeric DNA loss, is active in most tumours. Conflicting evidence has been published concerning the potential use of telomerase activity as a measurement of drug-induced tumour cell killing. In this study, the time courses of telomerase loss and induction of apoptosis were investigated in two testicular cell lines, Susa CP and 833 K, following 4-h exposure to cisplatin, melphalan or doxorubicin. Telomerase activity was only affected in both cell lines at 20 h following exposure to high concentrations of cisplatin (100x the drug concentrations causing 50% growth inhibition (IC(50) values)). The time course of melphalan-induced telomerase loss, which was again only apparent at 100x IC(50) concentrations, varied between the cell lines and doxorubicin (100x IC(50)) did not induce telomerase loss in either of the cell lines. Importantly, the levels and rates of appearance of apoptotic cells (nuclear morphology and annexin V staining) were similar for all three drugs in both cell lines; i.e. cisplatin, melphalan and doxorubicin (100x IC(50)) caused similar frequencies of apoptosis in Susa CP cells at 24 h whereas telomerase activities were 65, 123 and 96% of the control, respectively. The possibility that telomerase activity was lost following cisplatin treatment through a direct interaction of cisplatin with telomerase was discounted. Additionally, the relative levels of the RNA component of telomerase (hTR) and mRNA for the telomerase catalytic subunit (hTERT) were not related to the observed decreases in telomerase activity. These data indicate that telomerase activity is not a reliable indicator of chemosensitivity in human testicular cancer cells. Furthermore, cisplatin-induced loss of telomerase activity is not due to a direct reaction with the enzyme or decreased hTR levels.

Topics: Antineoplastic Agents; Apoptosis; Cisplatin; Doxorubicin; Drug Resistance, Neoplasm; Humans; Male; Melphalan; Reverse Transcriptase Polymerase Chain Reaction; Telomerase; Teratoma; Testicular Neoplasms; Tumor Cells, Cultured

Telomerase, a ribonucleoprotein, elongates and/or maintains telomeres by adding TTAGGG tandem repeat sequences using the RNA component of the enzyme as a template. Enzyme activity appears to be associated with cell immortalisation and malignant progression as telomerase activity has been found in the majority of human tumours, but not in most somatic cells or tissues. Telomerase inhibition has, therefore, been proposed as a novel and potentially selective target for therapeutic intervention. Since telomeric tandem repeats as well as the human telomerase RNA component (hTR) and its gene are guanosine-rich, we examined whether the sequence specific, G-Pt-G, cross-linking agent cisplatin is capable of inhibiting telomerase activity. The TRAP assay was used to measure telomerase activity in cisplatin treated cell extracts and RT-PCR strategies used to examine hTR expression after drug exposure. Cisplatin reduced telomerase activity in a specific and concentration-dependent manner in human testicular tumour cells, whilst doxorubicin, bleomycin, methotrexate, melphalan and transplatin had no effect. It is proposed that telomerase inhibition might be a component of the efficacy of cisplatin in the treatment of testicular cancer.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Cisplatin; Genetic Techniques; Humans; Male; Melphalan; Mice; Polymerase Chain Reaction; Stereoisomerism; Telomerase; Telomere; Testicular Neoplasms; Tumor Cells, Cultured

The authors describe 4 cases of multiple myeloma that developed one or more extraskeletal localizations. They have evaluated the relation between the onset of the extraskeletal localizations and the following myeloma characteristics: tumor burden, clinical phase, chemotherapy response, prognostic significance. All the patients showed these localizations in a plateau phase of myeloma. None of the patients had fever, pancytopenia and in no one the performance status worsened. All patients obtained at least a partial reduction of the localization and only the patient with the retro-orbital localization, got worse and died for myeloma. The other three patients are alive and do not show any sign of progression.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Laryngeal Neoplasms; Male; Melphalan; Middle Aged; Multiple Myeloma; Orbital Neoplasms; Prednisone; Prognosis; Stomach Neoplasms; Testicular Neoplasms; Vincristine

236 patients with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of cisplatin everyday, the patients were divided into 4 groups: 1. 20 mg/day x4-5, 80 cases; 2. 30 mg/day x3-5, 91 cases; 3. 40 mg/day x3-4, 37 cases; 4. 50 mg/day x2-3, 28 cases. Each group was repeated for 3 weeks. The effect and toxicity were analysed and compared with 22 cases treated by single DDP in 1975. The response (CR + PR) rate was 39.2% in 194 evaluated patients. The response rate was similar in group 20 mg and single DDP (29.2% and 27.3%). The response rate was lower than that of group 30 mg, 40 mg, and 50 mg (43.4%, 42.4%, and 50%) (P less than 0.05). The remissions in various groups were not significantly different. The toxicity of combined chemotherapy was not severe. 91.1% of patients had nausea and vomiting. There was no statistical difference in the various groups. Bone marrow suppression was less in single DDP group than that of combined chemotherapy group, (P less than 0.05). DDP 30 mg-50 mg 1/d x5-3 was better than HD-DDP in some patients.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Female; Fluorouracil; Humans; Lomustine; Lung Neoplasms; Male; Melanoma; Melphalan; Methotrexate; Middle Aged; Neoplasms; Procarbazine; Testicular Neoplasms; Vincristine

The pharmacokinetics of the alkylating agent melphalan was determined in a dialysed patient, 30 years old, who underwent unilateral orchidectomy for a malignant testicular tumor. Melphalan was included in a polychemotherapy treatment with eight 1-h infusions of 230 mg of etoposide (VP 16), then one 5-min infusion of 370 mg of melphalan (200 mg/m2) followed by autologous bone marrow grafting (ABMG). In this patient, melphalan pharmacokinetics was different from that of patients without important renal dysfunction for the area under the concentration curve (1,324 mg.l-1.min). However, with a melphalan elimination half-life of 80 min, ABMG could be performed, as usually, 24 h after melphalan administration. Plasma alpha-fetoprotein (AFP) concentrations showed that chemotherapy was efficient. Furthermore, we observed a modification of etoposide kinetics due to melphalan.

Topics: Adult; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Humans; Kidney Failure, Chronic; Male; Melphalan; Teratoma; Testicular Neoplasms

The patient was a 26-year-old male. He was admitted to our hospital with a chief complaint of hemoptysis, cough and left scrotal mass on May 9,1984. Chest X-ray film, LAG and CT revealed multiple lung, lymph node and cerebral metastases. Based on a diagnosis of testicular neoplasm, orchiectomy was performed on May 14,1984. PVB chemotherapy (Cis-diamminedichloro-platinum, Vinblastine and Pepleomycin) was administered. Because he got worse, however, he was treated with another combination chemotherapy, consisting of Methotrexate (MTX, 100 mg/m2 intravenous push (i.v.), 200 mg/m2 12-h infusion, day 1. The dose of MTX was increased with each course. Maximum dose of MTX was 900 mg/m2/day), Vincristine (1.0 mg/m2 i.v. day 1.) Actinomycin D (10 micrograms/kg i.v. days 3.4.5), Cyclophosphamide (600 mg/m2 i.v. day 3.), Adriamycin (30 mg/m2 i.v. day 8.) and Melphalan (6 mg/m2 p.o. day 8.). After 6 courses of this regimen, distant metastases disappeared or were reduced to under one tenth, and complete remission was obtained without severe side effects. The patient was in good health on March 30, 1985.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Doxorubicin; Drug Administration Schedule; Humans; Lung Neoplasms; Male; Melphalan; Methotrexate; Testicular Neoplasms; Vincristine

Topics: Aged; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Dysgerminoma; Humans; Male; Melphalan; Testicular Neoplasms; Transplantation, Autologous

Topics: Adenocarcinoma; Bleomycin; Carcinoma, Squamous Cell; Castration; Dactinomycin; Estrogens; Female; Humans; Kidney Neoplasms; Male; Melphalan; Nitrosourea Compounds; Phosphorus Isotopes; Plicamycin; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms; Vinblastine; Vincristine

Topics: Alkylating Agents; Antineoplastic Agents; Chlorambucil; Cyclophosphamide; Dactinomycin; Dysgerminoma; Humans; Male; Mechlorethamine; Melphalan; Methotrexate; Nitrofurazone; Pharmaceutic Aids; Plicamycin; Prognosis; Testicular Neoplasms; Testis; Vincristine

Topics: Adult; Antineoplastic Agents; Bence Jones Protein; Hodgkin Disease; Humans; Immunoglobulin D; Male; Melphalan; Plasma Cells; Plasmacytoma; Radiotherapy; Skin Neoplasms; Testicular Neoplasms

Topics: Adult; Antibiotics, Antineoplastic; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Dysgerminoma; Humans; Male; Melphalan; Methotrexate; Plicamycin; Prognosis; Teratoma; Testicular Neoplasms

Topics: Adolescent; Aged; Bone Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Neoplasms; Ovarian Neoplasms; Sarcoma, Ewing; Testicular Neoplasms; Thrombocytopenia; Tonsillar Neoplasms; Uterine Neoplasms

Topics: Chlorambucil; Dactinomycin; Drug Synergism; Humans; Male; Melphalan; Methotrexate; Oral Manifestations; Testicular Neoplasms

Topics: Adult; Antibiotics, Antineoplastic; Cyclophosphamide; Dactinomycin; Depression, Chemical; Dysgerminoma; Humans; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Olivomycins; Teratoma; Testicular Neoplasms

Topics: Adolescent; Adult; Dysgerminoma; Humans; Leukopenia; Lung Neoplasms; Lymphatic Metastasis; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Teratoma; Testicular Neoplasms; Vinblastine

Topics: Carcinoma; Cecal Neoplasms; Cobalt Isotopes; Female; Fibrosarcoma; Humans; Kidney Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Maxillary Neoplasms; Melanoma; Melphalan; Multiple Myeloma; Myxosarcoma; Palliative Care; Radioisotope Teletherapy; Testicular Neoplasms

Topics: Alkylating Agents; Bone Neoplasms; Cyclophosphamide; Dysgerminoma; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Mechlorethamine; Melphalan; Neoplasm Metastasis; Testicular Neoplasms

Topics: Adult; Disorders of Sex Development; Estrogens; Female; Genitalia, Female; Gonads; Hirsutism; Humans; Karyotyping; Male; Melphalan; Testicular Neoplasms; Testis

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Drug Synergism; Dysgerminoma; Humans; Male; Melphalan; Methotrexate; Olivomycins; Teratoma; Testicular Neoplasms

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

Topics: Adult; Cyclophosphamide; Dysgerminoma; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Melphalan; Mesothelioma; Middle Aged; Neoplasm Metastasis; Peritoneal Neoplasms; Radiotherapy Dosage; Sertoli-Leydig Cell Tumor; Teratoma; Testicular Neoplasms

Topics: Adolescent; Adult; Choriocarcinoma; Dysgerminoma; Female; Humans; Male; Melphalan; Methotrexate; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Pregnancy; Teratoma; Testicular Neoplasms; Vincristine

Topics: Female; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melphalan; Multiple Myeloma; Neoplasms; Osteosarcoma; Ovarian Neoplasms; Research; Sarcoma; Sarcoma, Ewing; Testicular Neoplasms; Thymoma

Topics: Choriocarcinoma; Dysgerminoma; Female; Humans; Male; Melphalan; Neoplasms; Ovarian Neoplasms; Pregnancy; Teratoma; Testicular Neoplasms

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: Humans; Lung Neoplasms; Male; Melphalan; Patient Discharge; Phenylalanine; Testicular Neoplasms

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