Continuous-infusion 5-fluorouracil in metastatic colorectal cancer patients pretreated with bolus 5-fluorouracil: clinical evidence of incomplete cross-resistance.
Explore the source record for details and available documents.
Colorectal Neoplasms↗
Biomedical subjects
C Cianci
Publications and source records attributed to C Cianci.
Oral doxifluridine in elderly patients with metastatic colorectal cancer: a multicenter phase II study.
BACKGROUND: Cancer chemotherapy in elderly patients is an important and under-researched area. Doxifluridine is a fluoropyrimidine derivative and is activated to 5-fluorouracil by uridine phosphorylase, which is more highly expressed in malignant cells. Because of the high bioavailability and low toxicity of oral doxifluridine we conducted this phase II trial to evaluate the feasibility, toxicity and activity of a home therapy with oral doxifluridine in elderly metastatic colorectal cancer patients. PATIENTS AND METHODS: Forty-three elderly metastatic colorectal cancer patients entered the study: their median ECOG performance status was 1 (0-2) and median age 74 years (69-83), the predominant site of metastasis was liver and all but one of the patients had received no previous chemotherapy. Doxifluridine was given orally at the initial daily total dose of 2250 mg for 4 consecutive days every week. The daily dose was reduced to 1500 mg if toxicities greater than grade 2 (WHO) occurred. RESULTS: Forty-two patients are evaluable for toxicity: treatment was well tolerated, with the most common side effect being diarrhea, severe in 7 (17%) patients (6 grade 3 and 1 grade 4). Thirty-six patients are evaluable for response and 2 complete and 3 partial responses have been observed (response rate 14%; 95% confidence limit interval 5%-29%). CONCLUSIONS: This study demonstrates that a home therapy with oral doxifluridine in elderly advanced colorectal cancer patients is feasible, with a relatively low rate of toxicity, and has moderate activity, comparable to that of intravenous 5-fluorouracil. Therefore, this treatment may be considered for the management of advanced colorectal cancer in the elderly.
Administration, Oral↗
Double 5-fluorouracil modulation with folinic acid and recombinant alpha-2B-interferon. A phase I-II study in metastatic colorectal cancer patients.
Twenty-two patients with metastatic colorectal cancer entered a Phase I-II trial to assess the maximum tolerable dose of alpha-2B-interferon administered intramuscularly three times per week in combination with fixed doses of 5-fluorouracil (450 mg/m2 IV for 5 days, and, from day 28, weekly) and folinic acid (200 mg/m2 IV before 5-fluorouracil) and the efficacy of this combination. Diarrhea and mucositis were the most frequent 5-fluorouracil-related toxicities and were > or = ECOG grade 3 in 23% and 18% of patients, respectively. Of 15 patients receiving interferon > or = 9 x 10(6) IU, 10 required interferon dose reduction mostly because of severe fatigue, anorexia, and declining performance status. Among 19 patients evaluable for response, 3 achieved a partial response and 1 a complete response for an overall response rate of 21% (95% confidence interval, 6-46%). In conclusion, our study demonstrates that IFN-alpha 2B at doses higher than 6 x 10(6) IU intramuscularly three times per week in the combination with 5-fluorouracil and folinic acid we used is too toxic for the majority of patients; this combination has moderate activity in metastatic colorectal cancer, although similar response rates have been reported, with less toxicity, with 5-fluorouracil plus folinic acid without IFN-alpha. A larger Phase III study would be required to determine the value of IFN-alpha in this combination.
Aged↗
Alpha-2B-interferon plus floxuridine in metastatic renal cell carcinoma. A phase I-II study.
BACKGROUND: Both alpha-interferon and floxuridine are active in metastatic renal cell carcinoma (MRCC); the two agents have demonstrated antitumor synergism and different clinical toxicities. The purpose of this study was to determine the maximum tolerable dose (MTD) of floxuridine (FUDR), administered as a constant continuous infusion for 14 days every 28 days, in combination with fixed doses of alpha-2B-interferon and to preliminarily evaluate the antitumor activity of this combination. METHODS: Sixteen patients entered the study; six had previously received alpha-interferon. Alpha-2B-interferon was administered at the dose of 10 x 10(6) IU intramuscularly 3 times/week and floxuridine at the starting daily dose of 0.075 mg/kg. This dose was escalated at each subsequent cycle up to dose-limiting toxicity. RESULTS: Most common toxicities included fever and flue-like symptoms, fatigue, anorexia, diarrhea, mucositis, and nausea, and 55% of patients experienced greater than or equal to Grade 2 toxicity, mostly diarrhea, for floxuridine doses greater than 0.125 mg/kg/d. Among 15 evaluable patients, 1 achieved a complete response and 4 achieved a partial one (33%; 95% confidence interval, 12-62%). Three partial responses were obtained in patients pretreated with alpha-interferon plus vinblastine. CONCLUSIONS: The combination of alpha-2B-interferon and floxuridine is feasible, and in our regimen the recommended daily dose of floxuridine for Phase II studies was 0.125 mg/kg. This combination is active in metastatic renal carcinoma, but further studies are needed to determine whether alpha-2B-interferon has added anything to the FUDR infusion or vice versa.
Adult↗
Two-photon spectroscopy in KCl using synchrotron radiation.
Explore the source record for details and available documents.
Journal Article↗
Na,K-ATPase co-distributes with ankyrin and spectrin in renal tubular epithelial cells.
Explore the source record for details and available documents.
Animals↗
ATP-dependent gelation contraction of microtubules in vitro.
Explore the source record for details and available documents.
Adenosine Triphosphate↗
ATP-induced gelation--contraction of microtubules assembled in vitro.
We report here an ATP-dependent formation and contraction, or syneresis, of a microtubule gel using microtubule proteins prepared from calf brains. Gel contraction is typically observable 15-30 min after ATP addition to microtubules assembled to steady state, and is complete after approximately 60 min, at which time the gel volume is reduced by as much as 75%. In contracted gels, microtubule bundles and aster-like structures are observable. Gelation-contraction requires only microtubule proteins present after purification by three cycles of assembly and disassembly.
Adenosine Triphosphate↗
p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen.
BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway.
Adult↗
Treatment options in patients with recurrent ovarian cancer.
The majority of patients with advanced ovarian cancer need a second-line treatment for recurrent disease after surgical cytoreduction and first-line chemotherapy. In these patients, treatment planning is mainly dependent on the platinum-free-interval. The patients may be distinguished as platinum-refractory (progression under platinum-based therapy), platinum-resistant (relapse within 6 months), or platinum-sensitive (relapse after 6 months). Patients with platinum-refractory or -resistant disease should be encouraged to enter clinical trials. Alternatively, these patients could receive tamoxifen or a non-platinum single-agent therapy. Since response rate and duration to different single-agents are similar, patient convenience, toxicities from prior treatment, side-effects and costs play a role in the drug selection for salvage chemotherapy. Patients with platinum-sensitive disease should receive carboplatin based or carboplatin-plus paclitaxel-based regimens. Secondary surgical cytoreduction may have a role in highly selected patients with good performance status, with long disease-free interval and without extra-abdominal or liver metastases.
Female↗