levoleucovorin and Kidney-Neoplasms

Currently, the backbone of therapy for metastatic disease is cytotoxic chemotherapy, along with the recent addition of targeted therapy based on molecular markers with KRAS testing. Despite the improvement in survival for metastatic colon cancer, newer agents are still needed. The clinical activity of TroVax in metastatic colon cancer has been studied in a small number of clinical trials. There is evidence that supports the vaccine's ability to induce humoral and cellular responses, as demonstrated by positive 5T4 and MVA-specific antibody titers and cellular proliferation assays. Future strategies should focus on investigating the immunomodulatory effects of chemotherapy in conjunction with TroVax, understanding the optimal dosing and schedule of the combination, and examining potential predictive biomarkers to determine which patients may benefit from immunotherapy from those who do not.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cancer Vaccines; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Colonic Neoplasms; Fluorouracil; Humans; Immunotherapy; Kidney Neoplasms; Leucovorin; Membrane Glycoproteins; Organoplatinum Compounds; Vaccination; Vaccines, DNA; Vaccinia virus

After over 30 years of theorizing, the use of angiogenesis inhibitors as anticancer therapy has finally moved from the realm of research to reality. Normal adult vasculature is generally quiescent in nature, with endothelial cells dividing approximately every 10 years. In contrast, the growth of tumours requires constant vascular growth and remodelling in order for solid tumours to grow beyond 1-2 mm3 in size. Vascular endothelial growth factor (VEGF) and its receptors are key regulators of the process of angiogenesis, which make them attractive therapeutic targets. A multitude of VEGF-targeted inhibitory agents are currently being investigated for the treatment of cancer. This review article focuses on recent developments in the use of angiogenesis inhibitors for the treatment of breast, lung, and colorectal cancers.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Camptothecin; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Fluorouracil; Humans; Hypertension; Kidney Neoplasms; Leucovorin; Lung Neoplasms; Neoplasms; Neovascularization, Pathologic; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

MTX-CF therapy was administered in 13 patients with advanced renal cell carcinoma. 2 patients were treated with MTX single agent therapy at a dosage of up to 750mg/m2 per cycle and a short CF rescue of 48 hours. They showed partial remissions along with severe toxicity including gastrointestinal symptoms and bone marrow depression. 11 patients were treated by combination of MTX/CF, vincristine, bleomycin and an alkylating agent (either peptichemio or cyclophosphamide). In this latter group, patients with a glomerular filtration rate of more than 70 ml/min received 150 to 400 mg/m2 per cycle MTX. Patients with decreased renal function (glomerular filtration rate less than 70 ml/min) received 35 to 100 mg/m2 per cycle MTX. Two out of 7 patients with decreased glomerular filtration rate achieved remissions of more than 50%, two achieved remissions of less than 50% and two patients achieved static disease. Only one patient in the group of 4 patients with normal renal function showed a remission of more than 50%. Median survival time of patients in partial remission or with static disease was 24 months, of patients showing progression was 5 months. This difference is highly significant (p < 0.001). These results seem to justify further investigations of MTX/CF therapy in hypernephromas, even in the presence of impaired renal function.

Topics: Adenocarcinoma; Alkylating Agents; Bleomycin; Drug Therapy, Combination; Humans; Kidney Neoplasms; Leucovorin; Methotrexate; Neoplasm Metastasis; Neoplasm Recurrence, Local; Vincristine

This phase I study was performed to evaluate the safety, tolerability, and efficacy of the oral matrix metalloproteinase inhibitor BAY 12-9566 in combination with 5-fluorouracil/leucovorin in patients with advanced solid tumours, and to identify the maximum tolerated dose and the dose for use in future studies.. BAY 12-9566 and 5-fluorouracil/leucovorin were administered to 17 patients in 3 cohorts. Each patient served as his/her own control, with 5-fluorouracil being given alone on days 1-5 of cycle 1. In cohort 1, BAY 12-9566 at 800 mg p.o. b.i.d. was given with 350 mg/m2 5-fluorouracil/20 mg/m2 leucovorin x 5 days q28 days. In cohort 2, the BAY 12-9566 dose was reduced to 400 mg p.o. b.i.d., with the 5-fluorouracil/leucovorin doses remaining unchanged. Finally, in cohort 3, BAY 12-9566 400 mg bid was given with 5-fluorouracil 400 mg/m2/day. Patients were continued on therapy until unacceptable toxicity or tumour progression occurred. Pharmacokinetic analyses for both BAY 12-9566 and 5-fluorouracil were performed.. The maximum tolerated dose was 400 mg p.o. b.i.d. BAY 12-9566 plus 5-fluorouracil/leucovorin at 400 mg/m2/day and 20 mg/m2/day, respectively. Thrombocytopenia necessitated a decrease of the dose of BAY 12-9566 by 50% from cohort 1 to cohort 2. Two dose-limiting toxicities occurred in cohort 3 consisting of neutropenic fever, and ileitis, causing severe diarrhea. Of 17 patients treated on study, 7 of 14 patients evaluable for response achieved stable disease. Pharmacokinetic analysis suggested there was no interaction between BAY 12-9566 and 5-fluorouracil.. BAY 12-9566 400 mg bid and 5-fluorouracil 350 mg/m2 plus leucovorin 20 mg/m2 can be co-administered. Although there is some evidence of a clinical interaction, there is no apparent pharmacokinetic interaction. Future studies with these 2 types of agents administered in combination are warranted.

Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Biphenyl Compounds; Canada; Cohort Studies; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Matrix Metalloproteinase Inhibitors; Maximum Tolerated Dose; Organic Chemicals; Phenylbutyrates; Safety; Salvage Therapy

Recent clinical trials have demonstrated activity of chemoimmunotherapy with interleukin-2 (IL-2), interferon-[alpha], and 5-fluorouracil (5-FU) in advanced renal cell cancer. A phase II study was performed to evaluate the affect of adding the potentiating agent leucovorin to this combination regimen. Treatment courses consisted of IL-2 5 MIU/m2 subcutaneously days 1, 3, and 5 of weeks 1 to 4, interferon-[alpha] 3 MIU/m2 subcutaneously on days 1, 3, and 5 of weeks 1 to 4, and leucovorin 50 mg/m2 IV followed by 5-FU 450 mg/m2 IV infusion weekly weeks 1 to 4. Patients were given no treatment on weeks 5 and 6 of the 6-week treatment cycle. Of the 20 patients enrolled in the study, 16 were evaluable for toxicity and 15 were evaluable for tumor response. The most severe toxicities included three reports of grade IV diarrhea; overall, nine incidents of grade III or IV toxicity were reported. No objective antitumor responses were observed, and the median time to progression was 2.8 months. We conclude that this combination chemoimmunotherapy regimen has substantial toxicity but no significant antitumor activity in patients with advanced stage renal cell carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Fluorouracil; Humans; Interferon-alpha; Interleukin-2; Kidney Neoplasms; Leucovorin; Middle Aged

To investigate the efficacy and safety of the FOLFOX-4 regimen for patients with metastatic renal cell carcinoma (MRCC).. Fifty-nine patients (median age 59 years) pre-treated or not by cytokines (29 vs. 30) received the FOLFOX-4 regimen every 2 weeks.. Three minor responses, and no complete or partial responses were obtained. The median progression-free survival was 3 months (95% CI: 2.6-3.4), the median survival 10.6 months (95% CI: 8.7-12.4), with no difference between pre-treated patients and others. Treatment was well tolerated.. The FOLFOX-4 regimen is ineffective in patients with MRCC. We believe that oxaliplatin should no longer be explored in renal carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Female; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Prognosis; Safety; Treatment Outcome

In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid.. Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated.. Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years.. In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Topics: Aged; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Intravenous; Kidney Neoplasms; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Palliative Care; Prognosis; Prospective Studies; Survival Rate

The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma.. Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity.. The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate.. The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Female; Fluorouracil; Follow-Up Studies; Humans; Kidney Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Survival Rate; Urinary Bladder Neoplasms

Cimetidine is an H2-receptor antagonist used in the management of peptic ulcer disease and other hypersecretory gastrointestinal disorders. This agent has intriguing immunomodulatory characteristics. A phase II trial of cimetidine in 19 patients with advanced malignant melanoma yielded an objective response rate of 16%. Having demonstrated that cimetidine is active in malignant melanoma, the authors conducted a phase II trial of cimetidine, 800 mg twice daily by mouth, in patients with advanced renal cell cancer. Among the 31 eligible patients, only one (3.2%) achieved a regression. It was a partial regression lasting 93 days. Median time to treatment failure was 83 days. The combination of interferon alpha-2A (IFL-RA) and 5-fluorouracil (5-FU) has been shown to be synergistic against experimental cell lines in vitro. Citrovorum factor (CF) added to 5-FU has been shown to improve objective tumor response compared with single-agent 5-FU in patients with advanced colorectal cancer. Fluorinated pyrimidines have shown some activity against renal cell cancer. We conducted a phase II trial of the combination of CF at 20 mg/m2 intravenous push followed by 5-FU at 325 mg/m2 intravenously daily for 5 days every week with interferon alpha-2A 5 x 10(6) units/m2 subcutaneously on days 1, 3, 5 in patients with advanced renal cell cancer. Among the 31 eligible patients, only two (6.5%) achieved a regression. Both were partial regressions. Median time to treatment failure was 84 days. Neither regimen is recommended for further testing in patients with advanced renal cell adenocarcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Cimetidine; Female; Fluorouracil; Histamine H2 Antagonists; Humans; Interferon alpha-2; Interferon-alpha; Kidney Neoplasms; Leucovorin; Male; Middle Aged; Recombinant Proteins; Remission Induction; Survival Analysis

The best schedule for administering floxuridine (FUDR) has not yet been established. Duration of infusion, need (and dosage) of leucovorin (folinic acid, FA), and circadian timing need to be further specified. Nevertheless, FUDR delivery according to circadian rhythms has allowed increase of dose intensity without enhancing the side effects. A 5-day infusional schedule combining FUDR and L-FA was devised as an attempt to increase dose intensity and to provide therapy every 3 weeks to patients with advanced cancer. An ambulatory programmable-in-time pump was used for this purpose. Fourteen patients entered this trial. Two dose levels (mg/kg x 5 days) were evaluated: 0.5 mg/kg/day in six patients and 0.525 mg/kg/day in eight patients. Both patient groups received a concurrent infusion of L-FA 10 mg/m2/day i.v. The delivery patterns of both FUDR and L-FA varied sinusoidally during the 24 hours with a maximum at 18.00 hours. Courses were repeated every 3 weeks. Of 35 courses, treatment produced mucosites greater than grade 2 in only two of them. No severe diarrhea, the dose-limiting toxicity of FUDR when infused over 14 days, was encountered at the dose levels tested. This 5-day chronotherapy schedule allowed delivery of a larger amount of FUDR than the flat delivery described in a previous report. A daily dose of 0.525 mg/kg FUDR, combined with 10 mg/mg2 L-FA, with intraindividual dose escalation according to tolerance, is recommended for future investigations of the activity of this chronotherapy schedule.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Carcinoma, Renal Cell; Chronobiology Phenomena; Colorectal Neoplasms; Drug Administration Schedule; Feasibility Studies; Female; Floxuridine; Humans; Infusions, Intravenous; Kidney Neoplasms; Leucovorin; Male; Middle Aged; Neoplasms; Stomach Neoplasms

A total of 25 patients with metastatic renal cancer were treated on a phase II protocol with 5 days of continuous-infusion fluorodeoxyuridine (FUDR), (0.1 mg/kg daily) together with high-dose oral leucovorin (100 mg 4 h) and daily x6 high-dose interferon-alpha 2b (30 x 10(6) IU/m2). Despite the good performance status of the patients and the inclusion of 14 previously untreated patients in the cohort, no response was observed among the 20 evaluable patients. Toxicities included high fever, moderate anemia, transient leukopenia, transient and mild elevations of transaminases, and moderate to severe nausea, vomiting, diarrhea, and mucositis. There were also two episodes each of confusion, fluid retention, and pancreatitis and one episode of increased creatinine levels. During the study three deaths occurred, two of which were possibly therapy-related. Despite previous reports of activity of FUDR in metastatic renal cancer, the present regimen cannot be recommended.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Combined Modality Therapy; Floxuridine; Humans; Infusions, Intravenous; Injections, Subcutaneous; Interferon-alpha; Kidney Neoplasms; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Time Factors

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Evaluation; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Kidney Neoplasms; Leucovorin; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Recombinant Proteins

Topics: Adult; Aged; Clinical Trials as Topic; Female; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Myeloid, Acute; Lymphoma; Male; Methotrexate; Middle Aged

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Disease Progression; Fatal Outcome; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Male; Neoplasm Staging; Nephrectomy; Organoplatinum Compounds; Patient Care Management; Renal Insufficiency; Tomography, X-Ray Computed; Ureter; Ureteral Neoplasms; Urinary Diversion

No standard chemotherapy regimen for advanced urothelial cancer has been established, except for cisplatin-based regimens. We report the case of a patient with double primary cancer, urothelial carcinoma of the upper urinary tract and colorectal cancer, who underwent oxaliplatin-based chemotherapies.. A 56-year-old Japanese man presented to our hospital with the diagnosis of a left renal pelvic tumor and rectal cancer. Several examinations including ureteroscopic biopsy and computed tomography-guided biopsy were performed; however, the diagnosis of renal pelvic cancer could not be made. Because the rectal cancer had been growing during the course of examination, he underwent five cycles of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan. The volumes of both the rectal cancer and renal pelvic tumor drastically decreased. He then underwent pelvic evisceration with colostomy and ureterocutaneostomy. The histological diagnosis of the renal pelvic tumor was urothelial carcinoma. He is free of disease at 12 months after the treatment.. To the best of our knowledge, this is the first report describing a remarkable response to fluorouracil, leucovorin, oxaliplatin, and irinotecan therapy for renal pelvic cancer. We suggest fluorouracil, leucovorin, oxaliplatin, and irinotecan is an effective therapy for patients with advanced urothelial cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Renal Cell; Colostomy; Fluorouracil; Humans; Irinotecan; Kidney Neoplasms; Kidney Pelvis; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Treatment Outcome; Ureterostomy; Urologic Neoplasms; Urothelium

Topics: Aneurysm; Angiogenesis Inhibitors; Angiomyolipoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Liver Neoplasms; Middle Aged; Neoplasms, Second Primary; Tomography, X-Ray Computed

Blood-borne metastases to the kidneys from solid tumors have received little attention in the medical literature because they usually occur in a setting of advanced systemic disease, and renal involvement is a relatively minor cause of symptoms. Although the frequency of metastases to the kidney in cancer patients is 7-13% in large autopsy series, incidental discovery of a renal metastasis as the first manifestation of a primary tumor is a very rare event. The most common primary malignancy to involve the kidney is bronchogenic carcinoma,followed by breast and gastrointestinal cancers. In this article, we report a patient with left colon cancer and isolated metastasis to the right kidney at the time of initial diagnosis. Left hemicolectomy and right nephrectomy were performed. Adjuvant systemic chemotherapy consisting of 5-fluorouracil (5-FU) and folinic acid (FA) was given. 5-FU and FA were stopped after four cycles because metastases to the lung and liver occurred about 3 mo after the surgery during adjuvant chemotherapy. Capecitabine was started. The patient died 9 mo after the discovery of the isolated renal metastasis. Nephrectomy is more for diagnostic clarification in the setting of synchronous primary because it has no effect on survival and its effect on quality of life is minimal; as seen in our case, the other organ metastases rapidly occur and the survival is limited. Nephrectomy may also compromise the choice of chemotherapy agents that require renal clearance, thus a careful evaluation of renal functions is necessary if a nephrectomy is performed. In the matter of a decreased renal clearance,the doses of these drugs should be decreased or the choice should be reevaluated.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Deoxycytidine; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Male; Neoplastic Cells, Circulating; Nephrectomy

We report the results of a chemotherapy regimen combining oxaliplatin, 5-fluorouracil, and folinic acid in patients with metastatic renal cell carcinoma. The objective of this pilot study was to define the potential efficacy of this second-line combination in patients previously treated with interleukin-2 alone or in combination with interferon alpha. Fourteen patients with metastatic renal cell carcinoma in failure after immunotherapy were included in this trial. During treatment, patients received six chemotherapy courses (Folfox regimen) administered every 2 weeks. Each cycle combined oxaliplatin day (D) D1 and folinic acid plus 5-fluorouracil D1 and D2. At completion of treatment, no objective response was observed and two patients presented stable disease. This chemotherapy schedule in patients with metastatic renal cell carcinoma previously treated with immunotherapy does not seem to be effective.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Female; Fluorouracil; Humans; Immunotherapy; Interferon-alpha; Interleukin-2; Kidney Neoplasms; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Pilot Projects; Prognosis

The patient was a 71-year-old man who had been diagnosed as having a left renal pelvic cancer with liver metastasis. We performed total left nephroureterectomy with lymphnode cleaning and partial resection of the liver. Because abdominal CT 5 months after the operation revealed multiple metastasis of the liver, we performed chemotherapy with a regimen consisting of methotrexate 50 mg (intravenous injection), cisplatin 30 mg and pirarubicin 20 mg (intraarterial infusion), and leucovorin 3 mg (intramuscular injection), three times at intervals of 6 hours. Ten days after chemotherapy, CT revealed the disappearance of most of the liver metastatic lesions, and a partial response was obtained. We are now performing the regimen at an interval of a month to a month and one-half to control the metastatic lesions.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Hepatic Artery; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Injections, Intramuscular; Kidney Neoplasms; Kidney Pelvis; Leucovorin; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Methotrexate

Topics: Adenocarcinoma, Clear Cell; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Liver Neoplasms; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pleural Neoplasms

Three patients with lung metastases of renal cell carcinoma (RCC) were treated with a combination of interferon-alpha, leucovorin and 5-fluorouracil. All patients were male between 60 and 66 years and had been treated by nephrectomy prior to the combination therapy. Interferon-alpha was administered at the dose of 9 x 10(6) IU intramuscularly 3 times/week, leucovorin at 30 mg/m2 per day intravenously (day 1 to 5) and 5-fluorouracil at 500 mg/m2 daily by continuous infusion intravenously (day 1 to 5) followed by weekly bolus therapy. One patient achieved complete response for 17 months and the other two achieved stable disease for 6 and 16 months. Side effects related to this therapy were diarrhea, stomatitis, alopecia, leucocytopenia and thrombocytopenia. Grade 3 stomatitis occurred after the continuous administration of 5-fluorouracil in one patient; he recovered by discontinuation of 5-fluorouracil. Combination therapy with interferon-alpha, leucovolin and 5-fluorouracil might be effective for the treatment of lung metastases of RCC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Fluorouracil; Humans; Infusions, Intravenous; Interferon-alpha; Kidney Neoplasms; Leucovorin; Lung Neoplasms; Male; Middle Aged

Results of cytotoxic chemotherapy in metastatic renal cell carcinoma are not impressive. Remission rates range between 0 and 20%. One of the substances which show a marginal effect is 5-fluorouracil (5-FU). The cytotoxicity of 5-FU can be modulated by combination with folinic acid as shown in various cell lines and clinical trials. We were interested to see whether such a biomodulation also occurs in renal cell cancer. The antiproliferative effect of 5-fluorouracil on two human cell lines of RCC and its potentiation by folinic acid was investigated in a monolayer proliferation assay. It could be shown that folinic acid enhanced the cytotoxic potential of 5-FU 6-8-fold. Our results indicate that the combination of these two drugs in the treatment of metastatic renal cell cancer might lead to better response rates.

Topics: Carcinoma, Renal Cell; Cell Division; Cell Survival; Drug Synergism; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Tumor Cells, Cultured

Fluoropyrimidines, 5-fluorouracil (5-FU), and 5-fluorodeoxyuridine (FdUrd) are effective inhibitors of DNA synthesis. Inhibitory action is potentiated both in vitro and in vivo by the addition of leucovorin (LV; either the natural [6S] isomer or the mixture of the unnatural and natural [6R,S] isomers). The inhibition of DNA is subsequent to thymidylate synthase inhibition mediated by the formation of a covalently bound ternary complex consisting of 5-fluorodeoxyuridine monophosphate, 5,10-methylenetetrahydrofolate, and thymidylate synthase. In vitro exposure of cells to varying concentrations of [6R,S]LV or [6S]LV increases intracellular pools of the reduced folate cofactor. The effect of [6S]LV is both dose and time dependent. The in vitro effective concentration of [6S]LV is approximately 1 to 10 mumol/L, depending on cell type. While HCT-8 cells demonstrated optimal modulation of 5-FU and FdUrd cytotoxicity with 1 mumol/L of [6S]LV for 5 hours, the SE cells required higher doses of LV and longer exposure time. Thus, dependent on the cell type, higher concentration (10 mumol/L) and duration of exposure (greater than 5 hours) may be essential for an effective modulation of fluoropyrimidine action. Clinically, to achieve the concentration and conditions found optimal in an in vitro system, a dose of 500 mg/m2 by 5-hour infusion appears to be the present optimal dose and schedule of [6R,S]LV administration in combination with 5-FU.

Topics: Cecal Neoplasms; Drug Administration Schedule; Drug Synergism; Floxuridine; Humans; Ileal Neoplasms; Kidney Neoplasms; Leucovorin; Stereoisomerism; Tetrahydrofolates; Thymidylate Synthase; Tumor Cells, Cultured

A 56-year-old female underwent treatment with leucovorin and 5-fluorouracil for extensive metastatic moderately differentiated transitional cell carcinoma (TCC) of the renal pelvis. This resulted in a complete response for 20+ months. This combination has not been reported before in TCCs of the urinary tract and requires further exploration.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Kidney Neoplasms; Kidney Pelvis; Leucovorin; Lymphatic Metastasis; Middle Aged; Remission Induction

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m2 i.v. and 5-fluorouracil (5-FU): 370 mg/m2 i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evaluation in patients with RCC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Drug Evaluation; Female; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Male; Middle Aged

A regimen of high-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen was administered to 34 patients with metastatic renal cell carcinoma. No complete remissions were observed, but ten patients (30%) achieved partial remission and an additional 13 patients (39%) had stabilization of disease. The median survival of responding patients (110 weeks) was significantly longer than that of nonresponding patients. The addition of tamoxifen did not influence response or survival. This regimen was tolerated without significant toxicity. A prospective randomized study of the vinblastine and high-dose methotrexate regimen compared to the respective single agents seem to be indicated.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Drug Evaluation; Female; Hematologic Diseases; Humans; Kidney Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Random Allocation; Tamoxifen; Time Factors; Vinblastine

Topics: Adenocarcinoma; Female; Humans; Kidney Neoplasms; Leucovorin; Mediastinal Neoplasms; Methotrexate; Middle Aged; Tracheal Stenosis

Methotrexate-citrovorum factor (MTX-CF) therapy was administered to 20 patients with advanced renal cell carcinoma. Eight patients were treated with MTX-CF only. Two patients who received short-term rescue showed partial remissions along with severe toxicity including gastrointestinal symptoms and bone marrow depression. Twelve patients were treated with a combination of MTX-CF, vincristine, bleomycin, and an alkylating agent (either peptichemio or cyclophosphamide). In this latter group, patients with a glomerular filtration rate of greater than 70 ml/minute received 150-400 mg/m2/cycle of MTX. Patients with decreased renal function (less than 70 ml/minute) received 35-100 mg/m2/cycle of MTX. Two of seven patients with a decreased glomerular filtration rate showed partial remissions and four patients had static disease. One patient in the group of five with normal renal function showed static disease. None showed objective improvement. The median survival time was 25 months for patients with partial remission and static disease and 4.75 months for patients with progression. This difference is highly significant (P less than 0.0005). These results seem to justify further investigations of MTX-CF therapy in hypernephromas, even in the presence of impaired renal function.

Topics: Adenocarcinoma; Adolescent; Aged; Bleomycin; Cyclophosphamide; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Kidney Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Peptichemio; Vincristine

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Agents; Bone Marrow; Depression, Chemical; Humans; Kidney Neoplasms; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pyrimethamine

Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Bone Marrow Diseases; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chlorobenzenes; Drug Therapy, Combination; Erythema; Headache; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Myeloid, Acute; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pyrimethamine; Pyrimidines; Teratoma; Testicular Neoplasms

Topics: Cyclophosphamide; Drug Therapy, Combination; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Methotrexate; Neoplasm Metastasis; Vincristine

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