melphalan and Teratoma

Considerable progress is being made in the chemotherapy of some gynecologic cancers. A random study comparing postoperative irradiation therapy with chemotherapy shows the two to be equally effective. Chemotherapy has the advantages of added safety and of being much less expensive for the patient. Postoperative chemotherapeutic treatment with VAC of patients with embryonal carcinoma of the ovary can prevent recurrence of this frequently fatal tumor. In some patients with advanced embryonal carcinoma of the ovary, chemotherapy with VAC may produce permanent remissions. Combined irradiation and chemotherapy and vincristine and actinomycin-D may be curative for some patients with advanced sarcomas in the pelvis or abdomen. This treatment combination is associated with severe complications; however, some are preventable.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Dactinomycin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Pelvic Neoplasms; Sarcoma; Teratoma; 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

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

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

Autologous bone marrow rescue circumvents the major toxicity of most cancer chemotherapeutic agents. Melphalan is a particularly well suited agent for use with autologous bone marrow rescue and produces response in chemo-resistant tumours. Thirteen patients have been treated with high dose melphalan with autologous bone marrow rescue in this department. The aims of treatment were palliation, debulking of non-resectable tumours and curative adjuvant therapy. Three patients died of melphalan related toxicity. Of the remaining ten patients there were five partial remissions, one objective response, one complete remission, one with no response and two patients in whom the response is not yet assessable (adjuvant therapy). In our experience high dose melphalan is an effective means of killing tumour cells which are not sensitive to chemotherapy at conventional doses. It is recommended in young patients who have not had extensive previous radio- or chemotherapy, in the early stages of disease, with cure or prolonged remission the aim. High dose melphalan is not recommended in the older patient or in those with massive diseases and is no longer used with palliative intent.

Topics: Adenocarcinoma; Adolescent; Adult; Bone Marrow Transplantation; Female; Humans; Lung Neoplasms; Male; Melphalan; Middle Aged; Neoplasms; Osteosarcoma; Pelvic Neoplasms; Teratoma

Topics: Amphotericin B; Animals; Cell Line; Cell Survival; Doxorubicin; Drug Synergism; Female; Humans; Leukemia L1210; Melphalan; Mice; Ovarian Neoplasms; Teratoma

Topics: Adult; Antibiotics, Antineoplastic; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Dysgerminoma; Humans; Male; Melphalan; Methotrexate; Plicamycin; Prognosis; Teratoma; 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: Adult; Cyclophosphamide; Cystadenoma; Dysgerminoma; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Teratoma; Thecoma; Thiotepa

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: Adenocarcinoma; Chromium Isotopes; Cobalt Isotopes; Cystadenoma; Dysgerminoma; Female; Gold Isotopes; Granulosa Cell Tumor; Humans; Melphalan; Ovarian Neoplasms; Phosphorus Isotopes; Sertoli-Leydig Cell Tumor; Teratoma; Time Factors

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

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