levoleucovorin and Melanoma

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Bleomycin; Bone Marrow Transplantation; Carcinoma; Cells, Cultured; Child; Cisplatin; Clinical Trials as Topic; Colonic Neoplasms; Combined Modality Therapy; Cytarabine; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Hepatic Artery; Humans; Hyperthermia, Induced; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Mechlorethamine; Melanoma; Meningeal Neoplasms; Methotrexate; Neoplasms; Osteosarcoma; Peritoneal Cavity; Pleura

Twenty-eight patients with advanced malignant melanoma were treated with high dose methotrexate (HDMTX) and folinic acid (FA) rescue. Nineteen patients were treated with 6-hour infusions and 10 patients with 24-hour infusions. One patient in the 6-hour infusion group showed a partial response. In the 24-hour infusion group there were no responses but there was a significant increase in renal toxicity. It is concluded that HDMTX and FA rescue are not useful agents in the treatment of advanced malignant melanoma.

Topics: Adult; Clinical Trials as Topic; Female; Humans; Infusions, Parenteral; Leucovorin; Male; Melanoma; Methotrexate; Middle Aged; Skin Neoplasms

Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation.. Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients.. All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days).. Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Loss, Surgical; Camptothecin; Carcinoma, Hepatocellular; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Gastrointestinal Stromal Tumors; Hepatectomy; Humans; Laparoscopy; Length of Stay; Leucovorin; Liver Neoplasms; Liver Transplantation; Living Donors; Male; Melanoma; Middle Aged; Organoplatinum Compounds; Postoperative Complications; Retrospective Studies; Tissue and Organ Harvesting

A 59-year-old patient with a coexisting primary choroidal melanoma and colorectal cancer was treated with external beam radiation (EBR) of his choroidal melanoma and systemic chemotherapy with leukovorin/5 fluorouracil (FU) for treatment of his metastatic colorectal cancer. Eight months following EBR, he showed evidence of radiation retinopathy with macular edema. Optical coherence tomography (OCT) showed macular edema and subretinal fluid. Subsequently, systemic bevacizumab (5 mg/kg) was added to his leukovorin/5FU chemotherapy. After the addition of bevacizumab, OCT showed complete resolution of the macular edema and subretinal fluid.. Bevacizumab may have a role in the treatment of radiation retinopathy, but further investigation is needed before any definitive conclusions can be made.

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Bevacizumab; Choroid Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Macular Edema; Male; Melanoma; Neoplasms, Second Primary; Radiation Injuries; Radiotherapy; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Vitamin B Complex

The rationale for melanoma-specific antitumor agents containing phenolic amines is based in part on the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates. The phenolic amine compounds 4-S-cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) inhibited in situ thymidylate synthase activity in pigmented melanoma cell lines but had little or no effect on nonpigmented and nonmelanoma cell lines. Theophylline, a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, increased tyrosinase activity and potentiated the inhibition of in situ thymidylate synthase by N-Ac-4-S-CAP. The inhibition of in situ thymidylate synthase by both drugs in pigmented melanoma cells correlated with the inhibition of DNA synthesis and cell growth and was not due to an indirect effect caused by inhibition of the enzyme dihydrofolate reductase. 4-S-CAP inhibition of thymidylate synthase activity in cell free extracts required oxidation of the drug. In the presence of tyrosinase, the concentration causing a 50% inhibition of thymidylate synthase activity (IC50) in cell-free extracts was less than 10 microM, but no inhibition was observed in its absence, even at a drug concentration of 500 microM. Two reducing agents, dithioerythritol and glutathione, effectively blocked the inhibition of thymidylate synthase by oxidized 4-S-CAP. In pigmented melanoma cells containing the enzyme tyrosinase, the quinone-mediated mechanism of inhibition of DNA synthesis via inhibition of thymidylate synthase may be uniquely important in the expression of phenolic amine cytotoxicity.

Topics: Antineoplastic Agents; Cell Division; Cell-Free System; Cysteamine; DNA; Humans; Kinetics; Leucovorin; Melanoma; Monophenol Monooxygenase; Oxidation-Reduction; Phenols; Tetrazolium Salts; Theophylline; Thiazoles; Thymidylate Synthase; Tumor Cells, Cultured

Chloroquinoxaline sulfonamide (CQS), a chlorinated derivative of sulfaquinoxaline (SQ), inhibited proliferation of murine B16 melanoma cells, but only when relatively high drug concentrations (1 mM) were used. The inhibition of cell growth by CQS was at least partially reversible by incubation in drug-free medium. Incubation of melanoma cells with CQS was associated with an arrest of the cell cycle in G0/G1 as measured by flow cytometry. The drug slightly decreased uptake of radiolabeled deoxyuridine and thymidine after 24- and 48-hr incubation periods but increased nucleoside incorporation at 72 hr. No evidence of intercalation with DNA was found. Because SQ previously was reported to inhibit an aspect of folate metabolism, we investigated the possibility that CQS limits tumor cell growth by altering folate homeostasis. This appears unlikely, however, in view of the following observations: (1) the cytotoxic effects of CQS could not be reversed by folinic acid; (2) deoxyuridine suppression of thymidine incorporation was not affected by CQS treatment; (3) CQS did not inhibit dihydrofolate reductase from mammalian or bacterial sources; and (4) CQS toxicity in mice was not reduced by folinic acid. Experiments performed with analogues modified in the quinoxaline and para-amino phenyl functions indicated that tumor cell inhibition did not require preservation of the conventional sulfonamide structure.

Topics: Animals; Cell Division; Cell Line; Chromatography, High Pressure Liquid; Deoxyuridine; DNA; Flow Cytometry; Leucovorin; Melanoma; Mice; Quinoxalines; Sulfanilamides; Sulfaquinoxaline; Tetrahydrofolate Dehydrogenase; Thymidine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Floxuridine; Fluorouracil; Humans; Iliac Artery; Infusions, Intra-Arterial; Leucovorin; Male; Melanoma; Methotrexate; Middle Aged; Ovarian Neoplasms; Pelvic Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Methotrexate (MTX) shows consistent cytotoxicity for melanoma cells in vitro but it is ineffective in clinical use at equivalent concentrations in vivo. This apparent paradox has been investigated by cell culture techniques and results quantified by cell number. In an in vitro model of high dose MTX therapy followed by leucovorin rescue (HD-MTX-LCR) there was survival of both melanoma and choriocarcinoma cell lines but not of an acute lymphocytic leukaemia cell line. The 70H metabolite of MTX was identified by HPLC in plasma samples of melanoma patients treated by HD-MTX-LCR, in which MTX concentrations approximately 10(-5) M were maintained for 24 h. However, metabolism per se is unlikely to account for the lack of response to MTX clinically. In vitro 70H MTX (10(-7) - 10(-6) M) was two orders of magnitude less cytotoxic for melanoma than MTX (10(-9) - 10(-8) M). The cellular accumulation of [3H]-MTX, using a rapid gradient centrifuge technique for separation of melanoma cells from medium, was reduced in the presence of 70H-MTX. The results suggest that reduced cellular uptake of MTX combined with biochemical rescue of tumour cells may partially explain the paradoxical lack of clinical response of melanoma to the drug.

Topics: Animals; Cell Count; Cell Line; Cell Survival; Choriocarcinoma; Humans; Leucovorin; Leukemia, Lymphoid; Male; Melanoma; Methotrexate; Mice

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Child; Drug Evaluation; Drug Therapy, Combination; Folic Acid Antagonists; Head and Neck Neoplasms; Humans; Leucovorin; Leukocyte Count; Melanoma; Neoplasms; Platelet Count; Pyrimethamine; Sarcoma

High-dose methotrexate was given to 28 patients with advanced malignant melanoma who had previously failed to respond to two chemotherapy protocols. There were five instances of serious, but not fatal, toxicity. One patient has had an objective response and seven patients have had stabilization of disease with an average duration of 4 months.

Topics: Adult; Aged; Female; Humans; Intestinal Neoplasms; Leucovorin; Leukopenia; Male; Melanoma; Methotrexate; Middle Aged; Skin Neoplasms

Topics: Animals; Asparaginase; Breast Neoplasms; Carboxypeptidases; Child; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Head and Neck Neoplasms; Humans; Leucovorin; Leukemia; Lung Neoplasms; Lymphoma; Melanoma; Methotrexate; Neoplasms; Osteosarcoma; Tetrahydrofolates; Thymidine

A rapid propidium iodide staining method was used for analysis of single-cell suspensions of bone marrow and tumor biopsies by flow microfluorometry. With this technique, information on the proliferative status of target tissues can be obtained within 10 min of sample removal. DNA histograms and labeling index of sequential bone marrow biopsies from a patient with Stage IV diffuse lymphocytic leukemia and treated with 1-beta-D-arabinofuranosylcytosine infusion showed pronounced reduction in the percentage of cycling cells. In contrast, sequential tumor biopsies from a melanoma patient on methotrexate-citrovorum factor rescue therapy showed no changes. In sequential bone marrow biopsies of 3 patients on high-dose methotrexate-citrovorum factor rescue, initial accumulation of cells in G1-S (Day 1) was followed by a significant proliferative response (Days 4 to 7) and return to pretherapy values. In contrast, no recovery similar to that of the bone marrow was seen in tumor cells.

Topics: Antineoplastic Agents; Bone Marrow Cells; Cell Division; Cytarabine; Ethidium; Fluorometry; Humans; Leucovorin; Leukemia, Lymphoid; Melanoma; Methotrexate; Neoplasms; Staining and Labeling

In clinical studies performed during 111 infusions of high dose methotrexate (MTX) we have evolved a clinical and laboratory protocol which permits such therapy without prohibitive risk to the patient. The plasma MTX data obtained indicate that pharmacokinetic disposition is dose related during these infusions and that such data are useful in identifying patients at risk from serious toxicity.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Drug Therapy, Combination; Humans; Leucovorin; Melanoma; Methotrexate; Middle Aged; Neoplasms; Sarcoma; Soft Tissue Neoplasms

Surgical techniques for the selective administration of anti-cancer drugs is presented. These isolated-perfusion or intra-arterial infusion procedures have achieved significant palliation for many patients with advanced cancer. When used in conjunction with surgical excision of certain early skin cancers, such as aggressive forms of malignant melanoma of the extremities, improved cure rates may be achieved.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Drug Therapy, Combination; Extremities; Female; Head and Neck Neoplasms; Humans; Injections, Intra-Arterial; Leucovorin; Male; Melanoma; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Sarcoma; Sarcoma, Kaposi; Skin Neoplasms

Topics: Agranulocytosis; Antineoplastic Agents; Breast Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melanoma; Methotrexate; Osteosarcoma; Pancreatic Neoplasms; Radiography; Rectal Neoplasms; Rhabdomyosarcoma; Testicular Neoplasms; Thrombocytopenia

Topics: Antineoplastic Agents; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Fluorouracil; Head; Head and Neck Neoplasms; Humans; Leucovorin; Melanoma; Melphalan; Methotrexate; Mouth Neoplasms; Nasopharyngeal Neoplasms; Paranasal Sinus Neoplasms; Sarcoma; Thiotepa; Vinblastine

Topics: Brain Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Head and Neck Neoplasms; Humans; Leucovorin; Lung Neoplasms; Melanoma; Methotrexate; Neoplasms; Palliative Care; Pelvic Neoplasms