melphalan and Prostatic-Neoplasms

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Dacarbazine; Diethylstilbestrol; Doxorubicin; Estramustine; Fluorouracil; Humans; Hydroxyurea; Male; Melphalan; Methotrexate; Mitomycin; Mitomycins; Prednisolone; Procarbazine; Prostatic Neoplasms; Streptozocin; Vincristine

Nontaxane-based chemotherapeutic options in castrate-resistant prostate cancer (CRPC) are limited despite the long natural history of the disease. We carried out a phase 1 dose-escalation study of the alkylating agent melphalan with autologous stem cell transplantation, comparing rapid changes in circulating tumor cells (CTC) and prostate-specific antigen (PSA) as a measure of response.. Cohorts of individuals with advanced CRPC received high-dose intravenous melphalan, and autologous blood was returned to patients during treatment. The efficacy endpoints were the PSA reduction rate, CTC response, survival parameters, toxicity and whether reinduction of endocrine sensitivity occurred.. Twenty-four patients were recruited. Dose escalation was feasible with the highest dose cohort being reached. Of 23 individuals evaluable for response, 16 had a PSA response of more than 30%; of 11 patients with soft tissue disease, 4 achieved a partial response and 7 had stable disease. Patients with CTC counts that decreased to less than 5 within 2 weeks from the start of therapy had a longer overall survival (30.6 months vs. 15.3 months, P = 0.03) Treatment was associated with myelosuppression and frequent hospitalizations. In 20 patients after the study, hormone therapy was reintroduced when PSA increased again; response rates were high.. Autologous transplantation following high-dose alkylating agent chemotherapy induces responses but proved toxic, although dose escalation proved possible. The possibility of using CTCs to identify responders at two weeks may be used to justify such an intensive approach. Many individuals went on to further respond to both docetaxel and hormonal therapy.

Topics: Antineoplastic Agents, Alkylating; Cohort Studies; Combined Modality Therapy; Humans; Male; Melphalan; Neoplastic Cells, Circulating; Orchiectomy; Peripheral Blood Stem Cell Transplantation; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

Alkylating agents have been reported to yield response rates of up to 20% in hormone-refractory prostate cancer. Melphalan was studied in four small trials in which the drug was given orally. In this phase II trial, melphalan (30 mg/m2) was given intravenously every 28 days to 27 patients with hormone-refractory prostate cancer. Pharmacokinetic sampling was performed so as to describe the clearance of melphalan in this population and in an attempt to carry out pharmacodynamic modeling for toxicity and response. Prostate-specific antigen (PSA) was also assessed prospectively. No objective responses to this regimen were documented. The median survival for patients on this trial was 11.5 months. There was no correlation between drug clearance and measured creatinine clearance and no relationship between systemic exposure and toxicity. A decrease of > 50% in serum PSA that was sustained for > 6 weeks was documented in two patients, most notably in one patient who has survived for more than 29 months. Intravenous melphalan is not an active agent in hormone-refractory prostate cancer.

Topics: Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Half-Life; Hormones; Humans; Infusions, Intravenous; Male; Melphalan; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

This prospective randomized study in nonhormonally responsive adenocarcinoma of the prostate shows that response rates to melphalan vs cyclophosphamide groups were virtually identical.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cyclophosphamide; Fluorouracil; Humans; Male; Melphalan; Methotrexate; Prednisone; Prostatic Neoplasms; Random Allocation; Vincristine

Ethonafide is an anthracene-containing derivative of amonafide that belongs to the azonafide series of anticancer agents. The lack of cross-resistance in multidrug-resistant cancer cell lines and the absence of a quinone and hydroquinone moiety make ethonafide a potentially less cardiotoxic replacement for existing anthracene-containing anticancer agents. For this study, we investigated the anticancer activity and mechanism of ethonafide in human prostate cancer cell lines. Ethonafide was cytotoxic against three human prostate cancer cell lines at nanomolar concentrations. Ethonafide was found to be better tolerated and more effective at inhibiting tumor growth compared with mitoxantrone in a human xenograft tumor regression mouse model. Mechanistically, we found that ethonafide inhibited topoisomerase II activity by stabilizing the enzyme-DNA complex, involving both topoisomerase IIalpha and -beta. In addition, ethonafide induced a potent G(2) cell cycle arrest in the DU 145 human prostate cancer cell line. By creating stable cell lines with decreased expression of topoisomerase IIalpha or -beta, we found that a decrease in topoisomerase IIalpha protein expression renders the cell line resistant to ethonafide. The decrease in sensitivity to ethonafide was associated with a decrease in DNA damage and an increase in DNA repair as measured by the neutral comet assay. These data demonstrate that ethonafide is a topoisomerase II poison and that it is topoisomerase IIalpha-specific in the DU 145 human prostate cancer cell line.

Topics: Animals; Antigens, Neoplasm; Antineoplastic Agents; Cell Cycle; Cell Line, Tumor; Cell Survival; DNA Breaks, Double-Stranded; DNA Topoisomerases, Type II; DNA-Binding Proteins; DNA, Catenated; DNA, Kinetoplast; Docetaxel; Humans; Isoquinolines; Male; Melphalan; Mice; Mice, SCID; Mitoxantrone; Naphthalimides; Prostatic Neoplasms; Protein Binding; Quinoxalines; RNA Interference; Taxoids; Topoisomerase II Inhibitors; Xenograft Model Antitumor Assays

Protein kinase C (PKC) has been implicated in propagating signals for apoptosis. We have investigated the effect of pharmacological modulation of PKC activity in DU-145 human androgen-independent prostatic carcinoma cells. The apoptotic death of these cells is characterized by the acquisition of classical apoptotic morphology and generation of > or = 1-mbp and 450- to 600-kbp DNA fragments in attached preapoptotic cell populations prior to cellular detachment and accrual of 30- to 50-kbp DNA fragments. We found that induction of apoptosis was arrested by downregulation of PKC activity and not by transient activation or inhibition of the enzyme. Concentrations and durations of exposure to phorbol esters that downregulated PKC activity correlated with inhibition of VP-16 or melphalan-induced morphological apoptosis and generation of the 30-to-50-kbp DNA fragments. Chronic exposure to phorbol-12,13-dibutyrate (PDBu) did not, however, suppress production of the > or = 1-mbp and 450- to 600-kbp DNA fragments found in preapoptotic cell populations, suggesting that PKC downregulation may interfere with the transition between a preapoptotic cell and an apoptotic cell. PKC isozyme analysis revealed that chronic PDBu treatment caused downregulation of PKC-alpha and -epsilon in DU-145 cells. Using concentrations of the PKC inhibitor UCN-01 that were consistent with PKC-alpha inhibition (but not PKC-epsilon inhibition), however, did not mimic the effects of chronic PDBu treatment, implying that downregulation of PKC-epsilon may be of particular importance. Together, these findings suggest that phorbol esters may act as tumor promoters by suppressing apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Carcinogens; Carcinoma; Cell Adhesion; Down-Regulation; Enzyme Activation; Etoposide; Gene Expression Regulation, Neoplastic; Humans; Male; Melphalan; Phorbol Esters; Prostatic Neoplasms; Protein Kinase C; Tumor Cells, Cultured

Higher order DNA fragmentation may be an essential signal in apoptosis. We found that etoposide (VP-16) induced apoptosis in human DU-145 prostatic carcinoma cells in a time- and concentration-dependent manner. Chromatin condensation was morphologically evident only when cells detached from the monolayer; untreated or VP-16-treated attached cells retained a normal morphology. We describe a radiolabeled alu-I sequence-based quantitative field inversion gel electrophoresis (QFIGE) method that permitted observation and quantification of discrete high molecular weight DNA fragments in detached (apoptotic) and attached (preapoptotic) DU-145 cells. The DNA fragments generated during the apoptotic death of these cells were > or = 1 (mega-base pairs) mbp, 450-600 (kilo-base pairs) kbp, and 30-50 kbp; we observed that these DNA fragments increased 9 +/- 2-, 8 +/- 2-, and 25 +/- 11-fold versus control, respectively, with a 24-hr exposure to 30 microM VP-16 in attached cell populations. In detached VP-16-treated cells, there was accrual of 30-50-kbp DNA fragments with a concomitant loss of the > or = 1-mbp and 450-600-kbp fragments; internucleosomal DNA cleavage was never observed. This pattern of high molecular weight DNA fragmentation was inhibited by cycloheximide treatment and was common to other apoptotic agents, including melphalan and bleomycin. These findings suggest that the > or = 1-mbp and 450-600-kbp DNA fragments are products of endonuclease activation and are not topoisomerase II/DNA interactions. Finally, the generation of the 30-50-kbp DNA fragments may mediate chromatin condensation, which characterizes apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Bleomycin; Cell Adhesion; Cell Line; Cyclophosphamide; DNA Topoisomerases, Type II; DNA, Neoplasm; Dose-Response Relationship, Drug; Electrophoresis; Etoposide; Humans; Kinetics; Male; Melphalan; Molecular Weight; Nucleosomes; Prostatic Neoplasms; Tumor Cells, Cultured

To test the hypothesis that elevated expression of the glutathione (GSH) salvage enzyme, gamma-glutamyl transpeptidase (gamma-GT) can confer resistance to chemotherapeutic agents, the cDNA for human gamma-GT was introduced into human prostate carcinoma cells by calcium phosphate precipitation. The sensitivity of a stable clone expressing an 18-fold increase in gamma-GT activity to melphalan (L-PAM), cisplatinum and doxorubicin was compared to that of the parent cell line and a clone transfected with gamma-GT cDNA in the antisense orientation. Despite increased gamma-GT expression and the ability of intact cells to metabolize exogenous GSH, transfection did not result in increased intracellular GSH levels even when an exogenous source of GSH was provided. Furthermore, no change in sensitivity attributable to the transfection and increased expression of gamma-GT was detected with any of the three drugs. Our data indicate that an increase in gamma-GT expression, exceeding that typically associated with resistance phenotypes, is not sufficient to confer resistance to L-PMA, cisplatinum or doxorubicin in the absence of other alterations in GSH homeostasis.

Topics: Cisplatin; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance; gamma-Glutamyltransferase; Humans; Male; Melphalan; Prostatic Neoplasms; Transfection; Tumor Cells, Cultured

Tumor cell resistance to many chemotherapeutic agents, including alkylating agents, cisplatin, and doxorubicin, is frequently associated with increased intracellular levels of the nonprotein sulfhydryl glutathione (GSH). Recent evidence has demonstrated that increased GSH levels can be accompanied by an increase in the activity of gamma-glutamylcysteine synthetase (GCS), which catalyzes the rate-limiting step in de novo synthesis of GSH, and by an increase in the steady state level of mRNA for the catalytic subunit of GCS. Using melphalan-resistant DU 145/M4.5 human prostate carcinoma cells, which express elevated GSH levels, GCS enzyme activity, and GCS mRNA levels, we sought to determine the mechanism(s) responsible for the increased GCS mRNA expression. As determined by Northern analyses and RNase protection assays, the steady state level of GCS message in the resistant cells was increased 10-20-fold, in comparison with the drug-sensitive parent DU 145 cells. No significant difference in gene copy number or evidence of rearrangement was detected in the resistant cell line by Southern analyses. The GCS-specific mRNA isolated from the resistant cells was less stable than that isolated from the drug-sensitive cells (half-lives of 6 hr and 9 hr, respectively), indicating that this difference does not contribute to the increased steady state levels in the resistant cells. Nuclear run-on experiments revealed that the GCS transcription rate in the DU 145/M4.5 cells was increased approximately 12-fold, in comparison with that detected in the DU 145 cells. This difference in transcription rate was comparable in magnitude to the difference in steady state mRNA levels detectable in the two cell populations. Similar correlations between steady state GCS mRNA levels and transcription rates were also observed in other DU 145 lines expressing intermediate degrees of resistance to melphalan and correspondingly intermediate GCS mRNA elevations. These data suggest that GCS expression is transcriptionally regulated in these melphalan-resistant tumor cells.

Topics: Drug Resistance; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glutamate-Cysteine Ligase; Humans; Male; Melphalan; Prostatic Neoplasms; Transcription, Genetic; Tumor Cells, Cultured; Up-Regulation

Prostate cancer that is androgen-insensitive is unresponsive to a wide spectrum of cytotoxic agents, including all of the alkylating agents. Since a major pathway for the detoxification of the alkylating agents is conjugation with glutathione (GSH), GSH depletion has proved to be effective as a technique to restore melphalan sensitivity in melphalan-resistant cancer cell lines. However, the effect of GSH depletion has not been widely studied in tumor cell lines that have not developed resistance due to previous exposure to alkylating agents. Thus, we decided to investigate GSH depletion as a technique to increase melphalan cytotoxicity to PC-3 cells, an androgen-insensitive prostate cancer line. After 2 and 6 h incubation with 0.25-5 microM melphalan, virtually no effect was observed on either clonogenic lethality or MTT viability until 5 microM exposures. A 24-h incubation of the cells with 100 microM buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, reduced the GSH content by 70%-75%. Following GSH depletion, an increase in clonogenic lethality and a decrease in MTT viability occurred after exposure to concentrations as low as 0.25 microM. The dose modification factor ranged from 2.9 after 2 h incubation to 4.5 at 6 h. These results provide support for additional studies in prostate cancer for further investigation of GSH depletion as a technique to induce sensitivity to alkylating agents in this chemotherapy-resistant tumor.

Topics: Buthionine Sulfoximine; Cell Survival; Glutathione; Humans; Male; Melphalan; Methionine Sulfoximine; Prostatic Neoplasms; Tumor Cells, Cultured

Glutathione (GSH) and glutathione-S-transferases (GST) have been implicated in resistance of tumor cells to certain alkylating agents, including melphalan. Glutathione levels and GST activities were determined in melphalan-resistant sublines of the human prostate carcinoma cell lines DU 145, PC-3 and LNCaP produced by serial treatment with melphalan at progressively increasing concentrations. The resistant sublines M4.5DU145, M5DU145, M6DU145, M6PC-3 and M6LNCaP were 27-, 7-, 3-, 6- and 2-fold more resistant to melphalan than the parental lines. The melphalan-resistant DU 145 and PC-3 lines showed cross-resistance to cisplatin and tetraplatin, but retained sensitivity to vinblastine, colchicine and etoposide. Interestingly, both sublines were also resistant to methotrexate and adriamycin. The melphalan-resistant LNCaP line showed slight resistance to cisplatin and adriamycin, but remained sensitive to tetraplatin and methotrexate. This line also retained sensitivity to vinblastine while developing resistance to colchicine. Intracellular GSH levels were increased 2.8 fold for M5DU145, 1.7 fold for M6PC-3 and 2.1 fold for M6LNCaP compared to the parental lines, whereas GST activity using chlorodinitro-benzene as a substrate was comparable for all lines. When cumene hydroperoxide was used as a substrate, an increase in GST activity was noted only in the M6PC-3 line as compared with the parent line. Western blot analysis showed no change in GST isozyme profile between parent and resistant DU 145 lines; however a mu class isoenzyme was detected in the resistant, but not in the parent PC-3 line, using a Yb1 antibody. M5DU145 cells maintained in the absence of melphalan for seven months maintained their resistance to melphalan. Depletion of GSH, with buthionine sulfoximine, to control levels reversed melphalan resistance to control levels.

Topics: Antineoplastic Agents; Blotting, Western; Buthionine Sulfoximine; Cell Division; Dose-Response Relationship, Drug; Drug Resistance; Glutathione; Glutathione Transferase; Humans; Male; Melphalan; Methionine Sulfoximine; Prostatic Neoplasms; Tumor Cells, Cultured

Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line.

Topics: Amino Acid Sequence; Animals; Anthraquinones; Antineoplastic Agents; Breast Neoplasms; Cell Membrane; Cell Survival; Cisplatin; Doxorubicin; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Melphalan; Methotrexate; Molecular Sequence Data; Oligopeptides; Orchiectomy; Pituitary Gland; Prostatic Neoplasms; Rats; Receptors, LHRH; Structure-Activity Relationship; Tumor Cells, Cultured

The biochemical and molecular basis for the elevation of glutathione (GSH) levels commonly detected in many drug-resistant cells has not been elucidated. In a series of L-phenylalanine mustard-resistant human prostate carcinoma cell lines (DU-145), resistance was associated with elevated GSH levels, increased activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH biosynthesis, and a marked increase in the steady-state levels of GCS-specific transcripts (4.0 and 3.2 kilobases). Loss of the resistant phenotype was accompanied by a reduction in GSH and a return of GCS activity and transcript levels to values comparable to those detected in the drug-sensitive parent cells. These data strongly implicate up-regulation of GCS activity as an important mechanism in the evolution of drug resistance associated with increased levels of intracellular GSH. The results further suggest that the ability to synthesize GSH may be more indicative of resistance than steady-state GSH levels per se.

Topics: Drug Resistance; Gene Expression; Glutamate-Cysteine Ligase; Glutathione; Humans; In Vitro Techniques; Male; Melphalan; Prostatic Neoplasms; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

Topics: Amino Acid Sequence; Animals; Breast Neoplasms; Cell Membrane; Chlorambucil; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Melphalan; Molecular Sequence Data; Ovulation; Pituitary Gland; Prostatic Neoplasms; Rats; Receptors, LHRH

To clarify the role of standard chest radiography in prostatic adenocarcinoma, the pulmonary manifestations of 198 patients with Stage D disease were evaluated. All patients were treated with chemotherapeutic protocols allowing for adequate clinical and radiographic correlation. Retrospective interpretation of serial chest radiographs revealed that 35% of our patients had visible intrathoracic abnormalities; however, only 24% of the patients had abnormalities attributable to intrathoracic metastases. Twenty-two percent of patients had pleural effusions, 16% reticular opacities, 3.5% reticulonodular opacities, 8% isolated or discrete pulmonary nodules, and 4.5% adenopathy. Etiologies of these opacities included metastatic disease in 93.5% of those with adenopathy and nodular or reticulonodular opacities, but 39% of pleural effusions and 52% of reticular opacities were best attributed to concomitant processes. Four patients had intrathoracic metastases without bone metastases. Standard chest radiography is a valuable screening procedure that should be correlated with clinical data to differentiate metastases from concomitant processes.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Fluorouracil; Humans; Lung; Lung Neoplasms; Lymphatic Metastasis; Male; Melphalan; Methotrexate; Middle Aged; Pleural Effusion; Prednisone; Prostatic Neoplasms; Radiography; Retrospective Studies; Vincristine

Topics: Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Estramustine; Fluorouracil; Humans; Hydroxyurea; Lomustine; Male; Melphalan; Methotrexate; Prednimustine; Prostatic Neoplasms

Topics: Acid Phosphatase; Aged; Drug Evaluation; Humans; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Remission, Spontaneous

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Humans; Male; Melphalan; Middle Aged; Prostatic Neoplasms; Remission, Spontaneous; Time Factors

Of 25 patients with estrogen-unresponsive prostatic adenocarcinoma submitted to multi-drug chemotherapy 6 had partial objective regression, 12 had objectively stable disease and 7 had progressive disease. The survival rates in the 3 groups were 63, 52 and 40 weeks, respectively.

Topics: Administration, Oral; Antineoplastic Agents; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Estrogens; Fluorouracil; Follow-Up Studies; Humans; Injections, Intravenous; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms; Vincristine

Topics: Adult; Aged; Carcinoma; Humans; Male; Melphalan; Middle Aged; Pilot Projects; Prostatic Neoplasms; Time Factors

Serial carcinoembryonic antigen (CEA) assays were conducted in patients with endocrine-unresponsive prostatic adenocarcinoma who were being treated with multidrug chemotherapy. Changes in CEA correlated with the clinical status of the patient in 70 per cent of the determinations and were more accurate than acid phosphatase in monitoring the response to treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Carcinoembryonic Antigen; Drug Therapy, Combination; Fluorouracil; Humans; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms; Vincristine

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: Adenocarcinoma; Bone Marrow; Centrifugation; Electrophoresis; Humans; Immune Sera; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulins; Male; Melphalan; Middle Aged; Multiple Myeloma; Prostatic Neoplasms; Protein Conformation

Topics: Adult; Cobalt Isotopes; Humans; Male; Melphalan; Multiple Myeloma; Prednisone; Prostatic Neoplasms; Radioisotope Teletherapy

Topics: Drug Therapy; Humans; Infusions, Parenteral; Male; Melphalan; Palliative Care; Prostatic Neoplasms