levoleucovorin and Carcinoma--Renal-Cell

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

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

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

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

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

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