levoleucovorin and Prostatic-Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Acinar Cell; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Pancreatic Neoplasms; Prostatic Neoplasms; Review Literature as Topic; Tomography, X-Ray Computed; Treatment Outcome

The current study evaluated the efficacy of oral uracil/tegafur (UFT) and leucovorin (LV) in patients with hormone-refractory metastatic prostate carcinoma.. Twenty-eight patients with hormone-refractory metastatic carcinoma of the prostate who had undergone antiandrogen withdrawal and no more than 1 prior chemotherapy treatment were enrolled on a single-institution Phase II trial. Patients were treated with oral UFT at a dose of 300 mg/m2/d and oral LV at a dose of 90 mg/day for 28 days followed by 7 days off therapy on a 35-day cycle regimen.. Twenty-six patients were evaluable for response and toxicity. There was no response by objective criteria in 9 patients with measurable disease. Four responses by prostate-specific antigen (PSA) criteria (i.e., PSA decrease by > 50%) were noted (15%) lasting a mean of 20.5 weeks. Therapy was generally well tolerated, with 2 patients developing Grade 4 toxicity (1 patient each with diarrhea and hand-foot syndrome) and 4 patients having significant Grade 3 toxicity (anemia, hyperbilirubinemia, and vomiting) (Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria). Six patients had stable disease by clinical, laboratory, and radiologic criteria for an average of 5 cycles of treatment (25 wks).. Although UFT and LV are generally well tolerated in the setting of hormone-refractory metastatic prostate carcinoma, the combination has a low level of activity. Its toxicity and activity is similar to that observed when intravenous 5-fluorouracil or capecitabine are given alone. It may be an option for further investigations in combination regimens.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Humans; Leucovorin; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Tegafur; Uracil

This report is a multi-institutional phase II study designed to obtain the response rate, survival, and toxicity profile for patients having hormone-refractory prostate cancer. Patients who had bidimensionally measurable prostate carcinoma in first or second remission after previous hormonal therapy but no history of chemotherapy were eligible. Patients were treated with leucovorin, 20 mg/m2 intravenously, followed by 5-fluorouracil (5-FU), 425 mg/m2 intravenously daily for 5 days, with cycles repeated every 28 days. Of 38 eligible patients, 3 (7.9%) had partial responses to therapy and 20 (52.6%) had stable disease. Median survival was 11.6 months for all 38 patients and median time to progression was 4.4 months. Most of the serious side effects were gastrointestinal or hematologic and overall, 23 of 38 patients (60.5%) experienced at least one grade 3 or 4 treatment-related toxicity of any type, as measured by the National Cancer Institute common toxicity criteria. Five patients (13.2%) withdrew from the study because of adverse reactions from chemotherapy. We conclude that treatment of hormone-refractory prostate cancer patients with 5-FU and leucovorin chemotherapy produced few responses at the cost of significant side effects. Further investigation of this combination is not warranted in this setting.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Survival Analysis

Results of cytotoxic chemotherapy for hormone-resistant prostate cancer are not impressive. One of the substances which seems to have a therapeutic benefit is 5-fluorouracil (5-FU). The effect of 5-FU can be modulated by addition of folinic acid (FA). We tested in a prospective, randomized phase II trial monotherapy with 5-FU versus the combination of 5-FU and high-dose FA.. 25 patients received 600 mg/m2 5-FU, and 24 patients 400 mg/m2 FA plus 600 or 400 mg/m2 5-FU. They were treated for two cycles for 5 days in a 21-day interval followed by a weekly single-day application until progression occurred. Pain remission, toxicity, time to progression and survival were evaluated.. Both regimens led to a pain remission in nearly 70% of the patients. Mucosal side effects like diarrhea and stomatitis occurred more often in the combination arm, whereas leukopenias were more frequent in the monotherapy are. We observed no statistically significant difference between the two treatment arms regarding time to progression and survival.. Although both regimens led to a pain remission, side effects are too severe to recommend these protocols for standard treatment of hormone-resistant prostate cancer.

Topics: Aged; Androgens; Antimetabolites, Antineoplastic; Drug Resistance, Neoplasm; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pain, Intractable; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Treatment Outcome

We performed a Phase II trial of oral leucovorin and high-dose fluorouracil (5FU) in hormone refractory patients with metastatic prostate cancer who had not had prior chemotherapy. 5FU was given as a 24-hour infusion at a dosage of 4 g/m2 and oral leucovorin at a dosage of 50 mg every 6 hours for four doses, starting with the infusion of 5FU. Fifteen patients were treated and three were not evaluable for response. There were no complete (CR) or partial responses (PR) in 12 evaluable patients (95% confidence interval for CR+PR of 0 to 26%). Three patients had stable disease and the remainder progressed. Toxicities were generally mild to moderate, but one patient died of sepsis while neutropenic. This dose and schedule of leucovorin and 5FU is not better than single-agent 5FU in patients with metastatic prostate cancer.

Topics: Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Survival Analysis

The response of hormone-refractory metastatic prostate cancer to chemotherapy is poor. The antitumour activity of single agent 5-fluorouracil (5-FU) is approximately 15%. Folinic acid is a reduced folate which when combined with 5-FU augments the activity of 5-FU by stabilizing the ternary complex of 5-deoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate, resulting in increased DNA inhibition and in increased cytotoxicity of 5-FU.. We used the combination of 5-FU at 300-370 mg/m2 and folinic acid at 200 mg/m2 daily for five days in 16 patients with hormone-refractory metastatic prostate cancer.. A total of 15 evaluable patients were treated. There were no complete or partial responses. Seven patients had stable disease. Diarrhea constituted the most common non-hematologic toxicities (67%). Four patients experienced grade 3 and 4 neutrophil toxicity. There was one treatment-related death from an acute enterocolitis and peritonitis in a patient with grade 4 neutropenia.. High dose folinic acid did not increase the cytotoxicity of 5-FU in hormone-refractory metastatic prostate cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Prostatic Neoplasms

To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m-2 day-1 x 5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m-2 day-1 x 5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6 h x 5.5 days) administered on a 28-day schedule in patients with stage D2 disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D2 prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Dipyridamole; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prostatic Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Metastasis; Neoplasms; Prostatic Neoplasms

Topics: Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Prostatic Neoplasms; Rectal Neoplasms

We report the case of an 84 years old prostate cancer patient with severe side effects after radiotherapy in 2006. He was cytogenetically analysed in 2009 and in 2012 in a comparative study for individual radiosensitivity of prostate cancer patients. No other patient had clonal aberrations, but this patient showed ring chromosomes in the range of 21-25% of lymphocytes. He received 5 cycles of 5-fluorouracil/folic acid for chemotherapy of sigmoid colon carcinoma in 2003, three years before radiotherapy of prostate cancer. Blood samples were irradiated ex vivo with Cs-137 γ-rays (0.7Gy/min) in the G0-phase of the cell cycle. 100 FISH painted metaphases were analysed for the control and the irradiated samples each. Multicolour in situ hybridisation techniques like mFISH and mBand as well as MYC locus, telomere and centromere painting probes were used to characterise ring metaphases. Metaphase search and autocapture was performed with a Zeiss Axioplan 2 imaging microscope followed by scoring and image analysis using Metafer 4/ISIS software (MetaSystems). In 2009 chromosome 8 rings were found in about 25% of lymphocytes. Rings were stable over time and increased to about 30% until 2012. The ring chromosome 8 always lacked telomere signals and a small amount of rings displayed up to four centromere signals. In aberrant metaphases 8pter and 8qter were either translocated or deleted. Further analyses revealed that the breakpoint at the p arm is localised at 8p21.2-22. The breakpoint at the q arm turned out to be distal from the MYC locus at 8q23-24. We hypothesise that the ring chromosome 8 has been developed during the 5 FU/folic acid treatments in 2003. The long term persistence might be due to clonal expansion of a damaged but viable hematopoietic stem cell giving rise to cycling progenitor cells that permit cell survival and proliferation.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blood Cells; Chromosome Aberrations; Chromosome Painting; Chromosomes, Human, Pair 8; Fluorouracil; Gamma Rays; Humans; In Situ Hybridization, Fluorescence; Leucovorin; Lymphocytes; Male; Metaphase; Prostatic Neoplasms; Ring Chromosomes

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Signet Ring Cell; Cetuximab; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Oxaliplatin; Prostatic Neoplasms; Radiography; Treatment Outcome

The aim of this study was to evaluate the feasibility of en bloc colorectal resection combined with radical prostatectomy as an alternative to total pelvic exenteration (TPE) for patients with locally advanced rectal cancer involving the lower urinary tract organs.. Twenty men with primary rectal cancer clinically involving the lower urinary tract organs underwent extended colorectal resection combined with radical prostatectomy. Data were entered prospectively into a database. Oncological and functional outcomes were analyzed.. Anal sphincter-preserving operation (SPO) with radical prostatectomy was performed in 12 patients, abdominoperineal resection with radical prostatectomy in 8, and urinary reconstruction in 16. Morbidity and mortality rates were 35.0% and 0%, respectively. Five-year overall and disease-free survival rates were 83.6% and 42%, respectively. The cumulative 5-year local recurrence rate was 20.0%. All patients with urinary reconstruction achieved good voiding function, and patients with SPO showed acceptable anal function.. For lower rectal cancers involving lower urinary tract, en bloc rectal resection combined with radical prostatectomy appears oncologically acceptable and can reduce the number of TPEs.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Feasibility Studies; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Organ Preservation; Plastic Surgery Procedures; Postoperative Complications; Prognosis; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate; Urinary Bladder Neoplasms

A 56-year-old man was hospitalized for anemia with appetite loss and body weight loss. He was diagnosed as advanced sigmoid colon cancer which invaded the rectal colon (Ra) and prostate (SI, N 0, P 0, H 0, M (-), cStage IIIa). We administered neoadjuvant chemoradiotherapy for fear of non-curative resection of the sigmoid colon and rectum after colostomy was performed. He was given radiation of the whole pelvis at a total dose of 39 .6 Gy (1.8 Gy x 22 times) combined with chemotherapy using continuous intravenous 5-FU (500 mg x 22 times). Two weeks after the chemoradiation, we administered chemotherapy (FOLFOX 4). Resectable resection was confirmed on Computed Tomography. We were able to conduct a low anterior resection of sigmoid colon and rectum. Postoperative histopathological examination of the resected sigmoid colon and rectum revealed no remnant cancer tissue. Neo-adjuvant chemoradiotherapy is considered to be effective for a study of non-curative resection of rectum.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Prostatic Neoplasms; Radiotherapy, Adjuvant; Rectal Neoplasms; Sigmoid Neoplasms

Cryosurgery must be performed in a manner that produces a predictable response in an appropriate volume of tissue. In present-day clinical practice, that goal is not always achieved. Concerns with cryosurgical techniques in cancer therapy focus in part on the incidence of recurrent disease in the treated site, which is commonly approximately 20-40% in metastatic liver tumors, and prostate cancers. Whether the cause of this failure is disease-based or technique related, cryosurgery for cancer commonly needs the support of adjunctive therapy in the form of anti-cancer drugs or radiotherapy to increase the rate of cell death in the peripheral zone of the therapeutic lesion where cell survival is in balance for several days post-treatment. Recent evidence has identified a third mechanism of cell death associated with cryosurgery. This mechanism, apoptosis or gene regulated cell death, is additive with both the direct ice-related cell damage that occurs during the operative freeze-thaw intervals and coagulative necrosis that occurs over days post-treatment. In this manuscript we discuss, through a combination of literature review and new data, the combined roles of these distinct modes of cell death in a prostate and colorectal cancer. Data are presented suggesting that sub-freezing temperatures, when sequentially applied with low dose chemotherapy, may provide improved cancer cell death in the freeze zone periphery. Since the mechanism of action of most common chemotherapeutic agents is to initiate apoptosis in cancer cells, the observation that sub-freezing exposures yields a similar effect provides a possible route toward molecular-based procedural optimization to improve therapeutic outcome.

Topics: Antineoplastic Agents; Apoptosis; Caspase Inhibitors; Caspases; Cell Death; Cell Line, Tumor; Cell Survival; Chemotherapy, Adjuvant; Cisplatin; Colorectal Neoplasms; Cryosurgery; Cryotherapy; Cysteine Proteinase Inhibitors; Fluorouracil; Humans; Leucovorin; Male; Necrosis; Prostatic Neoplasms; Time Factors

Uptake of 5-methyltetrahydrofolate into the PC-3 human prostate cancer cells was linear for the first 60 min. There was no difference in the initial rate of uptake in cells incubated in folate-free medium for 24 or 48 hr compared to control cells grown in folate-containing medium. The initial rate of 5-methyltetrahydrofolate uptake showed little dependence on extracellular pH and it was independent of extracellular sodium ions. Transport of 5-methyltetrahydrofolate into PC-3 cells was saturable - K(m) = 0.74 micro M and V(max) = 7.78 nmol/10(9)cells/min and these kinetic constants were not different in cells incubated for 24 hr in folate-free medium (K(m) = 0.80 +/- 0.22, V(max) = 8.52 +/- 0.50; P = 0.09, N = 3). Uptake of 5-methyltetrahydrofolate was inhibited by structural analogs with the K(i) values being 0.50, 1.79, and 31.8 micro M for 5-formyltetrahydrofolate, methotrexate, and folic acid, respectively. Uptake of 5-methyltetrahydrofolate was inhibited by the energy poisons, sodium cyanide, sodium arsenate, p-chloromercuriphenylsulfonate, and sodium azide. Uptake was inhibited by increasing concentrations of sulfate and phosphate ions, suggesting that 5-methyltetrahydrofolate may be transported by an anion-exchange mechanism. These results show that 5-methyltetrahydrofolate is transported into PC-3 prostate cancer cells by a carrier-mediated process.

Topics: Arsenates; Biological Transport; Carrier Proteins; Folic Acid; Humans; Hydrogen-Ion Concentration; Leucovorin; Male; Methotrexate; Phosphates; Prostatic Neoplasms; Sodium; Sodium Azide; Sodium Cyanide; Sulfates; Tetrahydrofolates; Tumor Cells, Cultured

The results of cytotoxic chemotherapy for advanced, hormone-escaped prostate cancer have been disappointing. Evaluation of the effect of new drugs or new combinations with already known ones is required. The antimetabolite 5-fluorouracil (5-FU) has been shown to be active in prostate cancer, acting via inhibition of thymidylate synthase, an essential enzyme in DNA de novo synthesis. Experiments with cell lines of different tumors have shown that 5-FU activity can be modulated by addition of the coenzyme tetrahydrofolic acid (folinic acid). We investigated the effect of folinic acid and its stereoisomers on 5-FU action in different cell lines of prostate cancer. It was found that addition of non-toxic folinic acid led to a two- to fourfold better antiproliferative effect of 5-FU. The unnatural 6R isomer, which is a compound of chemically synthesized folinic acid, inhibited the modulatory effect of the natural 6S isomer. Our results indicated that a combination of folinic acid and 5-FU may result in a better response of patients with hormone-resistant prostate cancer than of patients treated with 5-FU alone.

Topics: Antineoplastic Agents; Drug Synergism; Fluorouracil; Humans; Leucovorin; Male; Prostatic Neoplasms; Spheroids, Cellular; Stereoisomerism; Tumor Cells, Cultured

Combination effect of UFT and leucovorin against the rat prostatic carcinoma (R-3327) was evaluated by the subrenal capsular assay (SRCA) using nude mice. Anticancer effect of UFT was augmented by co-administration of both low and high dose leucovorin. These results suggest a clinical usefulness of UFT administration with leucovorin for the patients with hormonally refractory advanced prostatic carcinoma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Prostatic Neoplasms; Subrenal Capsule Assay; Tegafur; Tumor Cells, Cultured; Uracil

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

Topics: Ethinyl Estradiol; Humans; Leucovorin; Leukemia; Leukemia, Lymphoid; Lymphocytes; Male; Prednisone; Prostatic Neoplasms; Steroids