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F Cognetti

Publications and source records attributed to F Cognetti.

89 records · Page 5Linked to original sources
PubMed1990

Intraperitoneal recombinant alpha-2-interferon alternating with cisplatin as salvage therapy for minimal residual-disease ovarian cancer: a phase II study.

A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal (IP) recombinant alpha-2-interferon (r-alpha 2-IFN) and cisplatin (DDP) as salvage therapy for less than or equal to 5 mm residual-disease (RD) ovarian carcinoma. Fourteen assessable patients entered the study. All had received prior chemotherapy (11 with DDP-based regimens); five patients had macroscopic RD (less than or equal to 5 mm), and nine had microscopic RD (histologically positive random biopsies and/or positive cytology and immunocytochemical tests). The response to IP immunochemotherapy was evaluated by laparotomy. Pathologic complete remissions (PCRs) were achieved in seven patients (50%) who have remained free of disease with a median follow-up of 22+ months (range, 11+ to 30+ months). Six patients achieved a stable disease and one presented disease progression. With the exception of chemical peritonitis-induced adhesions, no limiting toxicity was observed. The results obtained in this small, highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous (IV) DDP. Larger comparative studies must be conducted to establish the potential role of IP DDP and r-alpha 2-IFN as compared with either of the single treatments.

Adult↗
PubMed1989

Prognostic factors for chemotherapy response and survival using combination chemotherapy as initial treatment of advanced head and neck squamous cell cancer.

Between May 1981 and December 1987, 152 consecutive patients with locally advanced and previously untreated head and neck squamous cell cancer (HNSCC) received two or three courses of neoadjuvant chemotherapy (NAC) prior to surgery and/or radiotherapy. Eighteen percent of patients achieved a complete response and 45% a partial response (PR), for an overall response rate of 63%. A variety of pretreatment patient and tumor characteristics were analyzed for both the tumor response to NAC and survival rate. Significantly higher CR rates were found in patients with a World Health Organization (WHO) performance status (PS) of 0 to 1 than in those patients with a PS of 2 (P = .03). Patients with stage III disease were significantly more likely to respond than those with stage IV (P = .006). Evaluation of all parameters through multivariate analysis identifies the tumor classification (P = .001) and the primary site (P = .006) as the most significant in predicting CR. The overall 5-year survival rate of the entire group of patients was 18% (median survival, 14.3 months). Analysis by PS (P = .001), stage (P = .002), and tumor (P = .001), and node (P = .01) classes showed significant differences. Patients achieving a CR after NAC had a significantly improved survival rate as compared with those with residual disease at assessment (P = .0003). With the multistep regression analysis, the tumor (P = .005) and node (P = .007) classifications, and the sex (P = .03) were significant factors, but CR (P = .0004) remained the most important and independent predictive factor. Randomized prospective trials are requested to clearly establish the role of NAC on survival rates.

Adult↗
PubMed1988

Neoadjuvant chemotherapy in previously untreated patients with advanced head and neck squamous cell cancer.

Between May 1981 and January 1986, 130 consecutive patients with advanced untreated head and neck squamous cell cancer (HNSCC) received neoadjuvant chemotherapy (NAC) with two or three courses of the CABO combination (methotrexate 40 mg/m2 intravenously (IV) on days 1 and 15; CDDP 50 mg/m2 IV on day 4; bleomycin 10 mg IV on days 1, 8, and 15; and vincristine 2 mg IV on days 1, 8, and 15 every 3 weeks) prior to surgery and/or radiotherapy. Of the 123 patients evaluable for response to chemotherapy, 19 (15.4%) had a complete remission and 59 (48%) a partial response, yielding a 63.4% overall response rate. Response rate was significantly correlated with the performance status (PS) (P = 0.001), the stage (P = 0.005), and the T class (P = 0.02); 107 patients completed subsequent local treatment (87 with radiotherapy and 20 with surgery +/- radiotherapy). The median survival of the 124 patients evaluable for survival was 14.7 months and the overall survival rate at 3 years was 24%. The median survival and the overall survival at 3 years for the surgical subgroup were 24.7 months and 38% and for the radiotherapy subgroup were 14.3 months and 22%. These results were compared with those obtained in a historical control group of 79 patients treated in our institute with short courses of chemotherapy regimens, which did not include cisplatin, followed by radiotherapy (29 patients) or local treatments alone (26 patients with radiotherapy and 24 patients with surgery +/- radiotherapy) between January 1976 and December 1980. Most of the patient characteristics were evenly distributed (age, sex, and primary sites) except that more advanced lesions were included in the NAC group (Stage IV: 85% versus 62%; T4: 65% versus 42%; N2-3: 48% versus 29%). The overall survival was significantly higher in patients receiving NAC than in the historical control group, comparing both the groups taken as a whole (P less than 0.05) and the surgery +/- radiotherapy (P less than 0.05) and the radiotherapy (P less than 0.02) subgroups. This experience suggests a positive role of NAC on survival. However, this improvement in outcome compared with a historical control group cannot be regarded as definitive evidence for benefit to patients. Randomized studies using active regimens are required to confirm these data.

Aged↗
PubMed1987

Combination chemotherapy with methotrexate, bleomycin, and vincristine with or without cisplatin in advanced squamous cell carcinoma of the head and neck.

A total of 185 eligible patients with advanced inoperable squamous cell carcinoma of the head and neck were randomized into two groups; the cisplatin, methotrexate, bleomycin, and vincristine (CABO) group received cisplatin (50 mg/m2; day 4), methotrexate (40 mg/m2; days 1, 15), bleomycin (10 mg; days 1, 8, and 15), and vincristine (2 mg; days 1, 8, and 15) and the ABO group received methotrexate, bleomycin and vincristine in the same doses on days 1, 8, and 15. After three courses, patients in both arms received weekly methotrexate as maintenance therapy; those 34 patients with previously untreated locoregional disease went off the study because of subsequent locoregional treatment in form of radiotherapy +/- surgery. The complete response rate was 16% in patients receiving CABO, compared with 5% among patients given ABO. The corresponding overall response rates were 50% and 28%, respectively (P = 0.003). Among patients with recurrent or metastatic disease, progression was delayed in patients receiving CABO (median, 18 weeks) compared to those receiving ABO (median, 14 weeks) (P = 0.07), but there was no difference in survival time. Myelosuppression consisted mostly of leukopenia, which was seen in 67% of the CABO patients versus 47% in the other arm. Myelosuppression-associated infection and hemorrhage led to death in two patients in the CABO treatment group and six patients in the ABO treatment group. Nausea and vomiting, mostly of grades 1 or 2, occurred in 93% of the patients given CABO and 44% of those receiving ABO. Other toxic effects--neuropathy, alopecia, stomatitis, constipation, fever/chills, diarrhea, cutaneous alterations, and renal impairment--occurred equally in the two treatment groups. This study underlines the role of cisplatin in head and neck cancer, although no impact on survival could be demonstrated. It also supports indirectly the superiority of combination chemotherapy over single-agent treatment for this disease.

Adult↗
PubMed1987

Alternating regimens in recurrent and metastatic squamous cell carcinoma of the head and neck.

In the present pilot study, two courses of CF and CABO combination chemotherapy were administered in an alternating manner to 27 patients affected with recurrent and metastatic squamous cell carcinoma of the head and neck. Of the 23 evaluable patients, 5 complete responses and 5 partial responses were observed; the overall response rate was 43.5%. Two out of five complete responders are still free of disease 30 and 65 weeks after the administration of CR. The toxicity of this program was tolerable and was carried out on an out-patient basis in all cases. The median survival of the entire group was 41 weeks (range 8-98.+). We conclude that these alternating regimens are not likely to produce better responses than other conventional cisplatin-including combinations, but they seem to significantly increase the duration of the response.

Antineoplastic Agents↗
PubMed1986

Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

Adolescent↗
PubMed1986

Phase II study of a combination of hydroxyurea, fluorouracil and mitomycin in previously treated squamous cell carcinoma of the head and neck.

Thirty-six evaluable patients with locoregionally recurrent or metastatic squamous cell carcinoma of the head and neck were treated with a combination of mitomycin (10 mg/m2 i.v. day 1), fluorouracil (500 mg/m2 i.v. days 1 + 8) and hydroxyurea (1 g/m2 orally days 2-14). Thirty-three patients had received prior radiation therapy and 34 prior chemotherapy. Only two patients exhibited a partial response. Hematological toxicity was substantial, with three patients experiencing leukopenia below 1000/mm3 and seven patients experiencing thrombocytopenia below 25,000/mm3. There were four cases of treatment-related bleeding and one infection. Other side-effects were mild to moderate. Low antitumor activity and substantial toxicity preclude further evaluation of this regimen in head and neck cancer.

Adult↗
PubMed1986

Maintenance of antiemetic effect of a metoclopramide-dexamethasone combination during subsequent cisplatin courses.

In two previous consecutive studies on antiemetic combination of metoclopramide and dexamethasone was found to be very active against nausea and vomiting induced by cisplatin (DDP; 50 mg/m2) alone or in combination with other cytotoxic emetogenic drugs. In the present study the activity of the same antiemetic combination has been followed in 18 patients during subsequent DDP courses. Twelve out of 18 patients (67%) had a complete control of the side effect after the first course of chemotherapy. No statistically significant differences were found as regards the intensity of nausea and vomiting, the patients' overall opinions and preference and the emesis duration. In conclusion this antiemetic combination can guarantee a high degree and long-term control of DDP-induced emesis at a dose of 50 mg/m2 given alone or in combination.

Adult↗
PubMed1984

Improved control of cisplatin-induced emesis with a metoclopramide-dexamethasone combination.

Twenty-four patients receiving combination chemotherapy including cisplatin at a dosage of 50 mg/m2 were entered on this antiemetic randomized open cross-over study. High-dose dexamethasone (DXM) (regimen A) was compared with the combination of DXM and high doses of metoclopramide (MCP) (regimen B). Five patients (20%) treated with regimen A and 13 (54%) treated with regimen B suffered neither nausea nor vomiting (P less than 0.05). Regimen B was found to be significantly more effective than regimen A for all the parameters of evaluation considered. No severe side-effects were observed.

Adult↗
PubMed1984

Randomized open cross-over trial between metoclopramide (MCP) and dexamethazone (DXM) for the prevention of cisplatin-induced nausea and vomiting.

Thirty-five patients receiving chemotherapeutic regimens including cisplatin (CDDP) were entered into a randomized open cross-over trial. Sixteen patients had previously received chemotherapy. Metoclopramide (MCP) was given i.v. in 4 doses of 1 mg/kg over a period of 4 1/2 hr, dexamethazone (DXM) was administered i.m. in 4 doses of 8 mg over 24 hr and another 10 mg i.v. just prior to CDDP administration. Sixteen patients who expressed a positive opinion on both previous antiemetics were given placebo (PLC). No significant differences were found between MCP and DXM, considering the mean score of both emesis intensity and patient's opinion. The mean duration of the symptoms was significantly longer with MCP than with DXM (P less than 0.02). Both antiemetic agents were more effective than PLC. No significant side-effects were observed. The results of this study indicate that both MCP and DXM provide a similar protection against CDDP-induced nausea and vomiting.

Adult↗
PubMed1981

The treatment of 48 patients affected by ovarian carcinoma at stages III and IV F.I.G.O.

The Authors analyzed the treatment of 28 patients in stage III (FIGO) and 20 patients in stage IV affected by epithelial ovarian cancer. In these cases, surgery was based on the criterion of cytoreduction and, where possible, maximum radicality. Within a month from surgery, all patients underwent a program of combined chemotherapy (VCR + 5 FU + CTX) envisaging successive cycles, every four weeks. Minimal side effects were generally observed. 13/28 (46.4%) responses were recorded in stage III and 4/14 (28.6%) in stage IV. The highest percentage of responses, 80%, was obtained in patients with a residual tumor less than 2 cm, all belonging to stage III. Stage III and stage IV patients with a residual tumor greater than 2 cm responded in 45% and 33% of the cases respectively. Patients who underwent explorative laparotomy showed negligible responses. There was a statistically significant difference survival between stage III and stage IV patients (p less than 0.001), among patients with a similar residual tumor greater than 2 cm, but in different stages (p less than 0.05), and among stage III patients who responded or not to chemotherapy (p less than 0.001).

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow?

Several chemotherapic agents, which are active against breast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps. Thymidine phosphorylase (TP) is the final enzyme responsible for Capecitabine activation. Studies have demonstrated that high intratumoral levels of TP and low levels of its catabolite dihydropyrimidine-dehydrogenase are correlated with the capecitabine response. The penetration of Capecitabine across the brain-blood barrier remains unknown; we report the case of and discuss a breast cancer patient who had an interesting response of brain metastases with Capecitabine in monochemotherapy before brain irradiation.

Adult↗
PubMedDate not supplied

Interleukin-2, interferon-alpha and interleukin-2 plus interferon-alpha in renal cell carcinoma. A randomized phase II trial.

BACKGROUND: The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rlL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 10(6) lU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-alpha at a daily dose of 6 x 10(6) IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity. RESULTS: Twenty-three percent (95% CI:+/-17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI:+/-11.9) and 9% (95% CI:+/-11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN. CONCLUSIONS: Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.

Adult↗