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F Caponigro

Publications and source records attributed to F Caponigro.

At least 37 records · Page 2Linked to original sources
PubMed1999

A phase II trial of cisplatin, methotrexate, levofolinic acid, and 5-fluorouracil in the treatment of patients with locally advanced, metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Induction chemotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) might improve survival with respect to radiation therapy alone. Furthermore, chemotherapy represents the only therapeutic option in metastatic head and neck carcinoma. METHODS: To improve further the results that could be obtained with an induction regimen of cisplatin (CDDP) plus 5-fluorouracil (5-FU), the authors treated 50 patients with locally advanced or metastatic SCCHN with a combination of CDDP 65 mg/m2 on Day 1, methotrexate 500 mg/m2 on Day 1, levofolinic acid 250 mg/m2 on Day 2, and 5-FU 800 mg/m2 on Day 2. Cycles were repeated every 2 weeks. The authors' aim was to increase the activity of CDDP plus 5-FU (PF) using a regimen that combined the three most active drugs in SCCHN and provided an adequate biochemical modulation of 5-FU, which was administered as an intravenous bolus infusion. RESULTS: Forty objective responses were observed among 50 evaluable patients (80%; 95% confidence interval [C.I.], 66-90%), including 7 complete responses (14%; 95% C.I., 5-27%), and 33 partial responses (66%; 95% C.I., 51-79%). Locoregional treatment, consisting of radiotherapy or surgery, was given at the end of chemotherapy. On completion of induction chemotherapy and locoregional treatment, 42 of 46 patients (91%) were rendered disease free. After a median follow-up of 20 months, the median duration of response was 10 months, the median failure free survival was 10 months, and the median overall survival was 21 months. The treatment was generally well tolerated. Grade 3-4 neutropenia occurred in 25 patients (50%), but it was febrile in only 3 patients. Nausea and vomiting were well managed with serotonin-3 blocking agents. Severe mucositis was seldom observed and easily manageable, and it never required hospitalization. CONCLUSIONS: The high level of activity, the manageable toxicity, and the noteworthy survival data of this regimen compare favorably with most of the drug combinations used worldwide to treat similar patient populations, with the additional advantage of significantly lower cost.

Adult↗
PubMed1999

First international conference on new molecular targets for anticancer therapy, Naples, 22-23 June 1998.

The First International Conference on New Molecular Targets for Anticancer Therapy was held in Naples on 22-23 June 1998, and represented an excellent occasion for discussing ongoing preclinical and clinical studies in the field of angiogenesis, signal transduction and antisense. In two general lectures, early clinical trials which are ongoing at EORTC and NCI, Bethesda, were summarized. Neoangiogenesis has been considered as a central pathogenic step in the process of tumor growth, invasion and metastasis. This complex process involves multiple steps and pathways dependent on the local balance between positive and negative regulatory factors, as well as interaction between the tumor, its vasculature and the surrounding extracellular matrix. Therapeutic agents and strategies are currently being devised to block one or more of the pathogenic steps involved in the process of tumor neovascularization or to directly target and destroy tumor vasculature. Since aberrant cell signaling plays a key role in the initiation, growth and progression of many tumors, signal transduction inhibitors may have a role as cytostatic agents. In addition, cancer sensitivity/resistance to conventional chemo/radiotherapy is largely dependent on cell signaling; hence its inhibition may induce a fundamental shift towards sensitivity. Thus, signal transduction inhibitors may play an important role also as modulators of conventional therapies, by shifting the balance towards pro-apoptotic signaling. Modulation of gene expression using oligonucleotides is currently an area of intense preclinical and clinical investigation. The effectiveness of antisense oligonucleotides as therapeutic agents depends, in addition to biological activity, on pharmacokinetics, tissue disposition, in vivo metabolic activity, elimination and safety profile. Probably the most clever way of using antisense oligonucleotides is to combine them with conventional chemotherapy, exploiting the different and possibly complementary mechanisms of action of the two treatment modalities.

Antineoplastic Agents↗
PubMed1999

Phase I-II study of gemcitabine and carboplatin in stage IIIB-IV non-small-cell lung cancer.

PURPOSE: Platinum-based chemotherapy currently represents standard treatment for advanced non-small-cell lung cancer. Gemcitabine is one of the most interesting agents currently in use in advanced non-small-cell lung cancer, and high response rates have been reported when it is administered in combination with cisplatin. The aim of the present study was to evaluate the combination of gemcitabine and carboplatin in a phase I-II study. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer received carboplatin at area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step. Gemcitabine was administered on days 1 and 8 and carboplatin on day 8 of the 28-day cycle. Dose escalation proceeded up to dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia or grade 3 nonhematologic toxicity. RESULTS: Neutropenia was DLT, inasmuch as it occurred in three of five patients receiving gemcitabine 1,200 mg/m2. Nonhematologic toxicities were mild. Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II studies. An objective response was observed in 13 (50%) of 26 patients, including four complete responses (15%) and nine partial responses (35%). Median duration of response was 13 months (range, 3 to 23 months). Median overall survival was 16 months (range, 3 to 26 months). CONCLUSION: The combination of gemcitabine and carboplatin is well tolerated and active. Neutropenia was DLT. The observed activity matches that observable in cisplatin-gemcitabine studies, whereas duration of response and survival are even higher. A phase II trial is under way.

Adult↗
PubMed1999

Phase I and pharmacokinetic study of tomudex combined with 5-fluorouracil plus levofolinic acid in advanced head and neck cancer and colorectal cancer.

In vitro studies have shown a schedule-dependent synergism between Tomudex and 5-fluorouracil (5-FU). Incubation of different types of head and neck and colorectal cancer cells with levofolinic acid (LFA) plus 5-FU for 4 or 24 h, after 24-h incubation with Tomudex, produces a clear synergism. The purpose of this study was to evaluate the tolerability and activity of a combination of Tomudex, LFA, and 5-FU in advanced head and neck and colorectal cancer. Furthermore, the potential for 5-FU pharmacomodulation by Tomudex was also evaluated through an intrapatient assessment of dihydropyrimidine dehydrogenase (DPD) activity and 5-FU AUC with and without pretreatment with Tomudex. Eligible patients were treated with Tomudex at the starting dose of 1.5 mg/m2 on day 1, LFA at a fixed dose of 250 mg/m2 on day 2, immediately followed by bolus 5-FU at the starting dose of 600 mg/m2. Tomudex and 5-FU doses were alternately escalated. Courses were repeated every 2 weeks. In the second course, LFA and 5-FU were administered on day 1 and Tomudex on day 2; further treatment was given according to the sequence used in the first course. Plasma 5-FU concentrations were analyzed on courses 1 and 2 using a high-performance liquid chromatography assay with UV detection. DPD activity was measured in peripheral blood mononuclear cells on courses 1 and 2 using incubation of cytosol with [14C]FU and quantitation of metabolite formation. Fifty-eight patients were enrolled in the study. Dose escalation was stopped at step 8, because of the occurrence of dose-limiting toxicity in two of three patients. The dose level immediately before (3 mg/m2 Tomudex, 1050 mg/m2 5-FU) was selected for further evaluation. Tomudex and 5-FU mean dose intensities actually delivered at the seventh step were 1.32 and 462 mg/m2/week, respectively. Six of 40 patients with metastatic colorectal cancer obtained an objective response (15%; 95% confidence interval, 6-30%). In particular, three complete responses and three partial responses were observed. Six of 17 patients with locally advanced or metastatic head and neck cancer obtained an objective response (1 complete response + 5 partial responses; 35%; 95% confidence interval, 14-62%). Median duration of response in colorectal cancer patients was 12 months. 5-FU AUC was not significantly different between the two courses (median intrapatient difference, 9.3%; P = 0.28). DPD activity in course 1 was significantly higher than course 2 (P = 0.041) in the 16 patients in which values were evaluable. The combination of Tomudex, LFA, and 5-FU is well tolerated and active in colorectal and head and neck cancer. The Tomudex mean dose intensity actually delivered is higher than usually achieved in monotherapy. The absence of a clear pharmacokinetic interaction suggests that the synergism of Tomudex and 5-FU might occur at the cellular level.

Adult↗
PubMed1998

Phase I/II study of paclitaxel and vinorelbine in metastatic breast cancer.

Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cancer no longer amenable to conventional treatment were entered into a phase I/II study in which the vinorelbine dose was fixed at 30 mg/sqm and paclitaxel was started at 90 mg/sqm and then subsequently escalated by 30 mg/sqm per step. Cycles were repeated every 21 days. Hematopoietic growth factor support was provided from the 4th dose level onwards. Grade III neutropenia was observed only in 2 patients treated at the 5th dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in all three patients treated at the 6th dose level. Other toxicities were mild. Paclitaxel 210 mg/sqm and vinorelbine 30 mg/sqm was the selected combination for phase II. Overall response rate in 34 evaluable patients was 38% (95% confidence interval (C.I.), 22% to 54%). In particular, 3 complete responses (9%) and 10 partial responses (29%) were observed. The observed level of antitumor activity, with an overall response rate of 38% and a median duration of response of 12 months, is of interest, since the study was targeted only to anthracycline-pretreated patients, most of whom had adverse prognostic features. The evaluation of a combination of vinorelbine and paclitaxel as first-line therapy in metastatic breast cancer seems worthwhile and is currently undergoing.

Adult↗
PubMed1998

Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study.

PURPOSE: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. METHODS: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour i.v. infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 microg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). RESULTS: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81% (26% CRs) in patients unpretreated for metastatic disease and 37% in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95% in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90% in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. CONCLUSIONS: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.

Adult↗
PubMed1997

Phase I study of vinorelbine and paclitaxel in small-cell lung cancer.

BACKGROUND: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs. PATIENTS AND METHODS: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which vinorelbine was given at a fixed dose of 30 mg/m2 by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial dose of 90 mg/m2, which was subsequently escalated by 30-mg/m2 steps. Cycles were repeated every 21 days. RESULTS: Grade 3 neutropenia was observed only in three patients treated at the fifty dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in three of five patients treated at the fifth dose level (paclitaxel 210 mg/m2). Other side effects were generally mild. The overall response rate in 22 evaluable patients was 32% (95% CI 13-51%); in particular, 1 complete response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended for phase II studies are 180 mg/m2 for paclitaxel and 30 mg/m2 for vinorelbine. The observed myelosuppression was less severe than anticipated on the basis of the effects of each drug alone. CONCLUSIONS: The promising activity of this drug combination warrants a phase II study in untreated patients with extensive-stage small-cell lung cancer.

Adult↗
PubMed1997

Fotemustine and dacarbazine plus recombinant interferon alpha 2a in thetreatment of advanced melanoma.

Forty-three consecutive patients with advanced melanoma not previously treated with cytotoxic drugs (22 of them had already received adjuvant recombinant interferon alpha 2a (rIFN alpha 2a)) were given a combination of intravenous (i.v.) fotemustine (FM), 100 mg/m2 on day 1, and dacarbazine (DTIC), 250 mg/m2 i.v. on days 2-5, every 3 weeks. rIFN alpha 2a was administered at the dosage of 3 MIU subcutaneously 3 times a week until progression. Four complete and 13 partial responses were registered, for an overall response rate of 40% (95% CI, 25-56%). Activity of this regimen was similar in patients with mainly visceral (10/22, 45%) or soft tissue (6/13, 46%) involvement. The median duration of responses was 24 weeks. Median survival time was 40 weeks, with a 13% 2 year survival rate. Neutropenia and thrombocytopenia affected 67% and 51% of patients, but were of WHO grade 4 in only 2% and 5% of them, respectively. Side-effects attributable to rIFN alpha 2a were mild and manageable. In conclusion, the combination of FM + DTIC and rIFN alpha 2a seemed well tolerated and relatively active in patients with advanced melanoma. However, the role of rIFN alpha 2a in affecting the long-term outcome of patients is still questionable.

Adult↗
PubMed1997

Protein kinase C: a worthwhile target for anticancer drugs?

Protein kinase C (PKC) is an enzyme family with serine/threonine kinase function which is involved in the transduction of signals for cell proliferation and differentiation. The important role played in processes relevant to neoplastic transformation, carcinogenesis and tumor cell invasion renders PKC a potentially suitable target for anticancer therapy. Bryostatin 1, a macrocyclic lactone isolated from Bugula nerutina, is a partial PKC agonist, and has shown potent antineoplastic properties in vitro and in vivo. Staurosporine, an alkaloid isolated from microbial sources, is ine of the most potent PKC inhibitors and has shown high antiproliferative activity in vitro, but poor selectivity. Staurosporine analogs have thus been synthesize with the aim of obtaining more selective PKC inhibition; among these, CGP 41251 has shown reduced PKC inhibitory activity, but a higher degree of selectivity when assayed for inhibition of different kinases. Several studies indicate a role for PKC in the regulation of the multidrug resistance (MDR) phenotype, since several PKC inhibitors are able to partially reverse MDR and inhibit P-glycoprotein (Pgp) phosphorylation. The MDR phenotype is also associated with variation in PKC isoenzyme content, in particular with PKC-alpha overexpression. While adequate PKC modulation might offer an attractive concept to modulate MDR, other potential mechanisms of PKC interaction with anticancer drugs exist and have been documented, such as the enhancement of chemotherapy-induced apoptosis by safingol, a specific PKC inhibitor. Three phase I clinical trials with bryostatin have been completed so far and have shown that myalgia is the dose-limiting toxicity, while some antitumor activity is evident. Safingol is presently undergoing a phase I clinical trial in combination with doxorubicin. While no definitive data are presently available, it appears that safingol plasma levels approach those associated with chemopotentiation in animals and no pharmacokinetic interaction between the two drugs exists. Drugs targeting PKC are well work considering for clinical trials, particularly for their potential as modulators of currently available cytotoxic agents.

Animals↗
PubMed1996

Accelerated split-course (type B) thoracic radiation therapy plus vinorelbine/carboplatin combination chemotherapy in stage III inoperable non-small cell lung cancer.

43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC.

Adult↗
PubMed1996

Modulation of chemosensitivity by alpha interferon in multiple myeloma and non-Hodgkin's lymphoma.

Low-grade non-Hodgkin's lymphoma and multiple myeloma are chemosensitive malignancies, but are rarely curable because of primary or acquired drug resistance. Interferon has been shown to modulate the multidrug resistance phenotype and to reinduce chemosensitivity in patients with chemoresistant tumors. Fifteen patients with multiple myeloma and 64 patients with low/intermediate grade non-Hodgkin's lymphoma unresponsive to initial chemotherapy were treated with alpha 2b interferon for 2 months. In case of an objective response, treatment was continued until disease progression; non-responding patients received the same chemotherapy to which they were resistant, preceded by a 5 day course of interferon. Interferon salvage monotherapy induced an objective response in 1/15 patients with multiple myeloma and in 7/64 patients with non-Hodgkin's lymphoma. An objective response was achieved after retreatment with first-line chemotherapy preceded by interferon in 4/14 patients (28.6%) with multiple myeloma and in 20/56 evaluable patients (35.7%) with non-Hodgkin's lymphoma. Toxicity was moderate, predictable, manageable, and never caused interruption of the treatment. Interferon appears to be able to modulate chemosensitivity of tumors refractory to chemotherapy with several potential mechanisms, including an effect on drug accumulation; its utilization in this setting warrants further evaluation.

Adult↗
PubMed1995

Phase II study of high-dose epirubicin, lonidamine, alpha 2b interferon in advanced breast cancer.

44 patients with advanced breast cancer were treated with high-dose epirubicin (130 mg/sqm), because of its steep dose-response curve. Lonidamine and alpha interferon were administered as well with the aim of increasing epirubicin uptake and overcoming drug resistance. Granulocyte-colony stimulating factor support was provided. 14 complete responses and 22 partial responses were observed in 40 evaluable patients for a 90% overall response rate. Median duration of response was 12 months for complete responders, 7 months for partial responders. In two cases the complete response has lasted for more than two years. Myelosuppression, infection, and cardiac toxicity were the main treatment-related toxic effects. These results are encouraging enough to justify a randomized comparison of our chemotherapy program with standard regimens used in advanced breast cancer.

Adult↗
PubMed1991

Second-line chemotherapy of advanced colorectal cancer with sequential high-dose methotrexate and 5-fluorouracil.

Twenty-five patients with pretreated advanced colorectal carcinoma were subjected to second-line chemotherapy with sequential high-dose methotrexate and 5-fluorouracil. In 20 evaluable patients 2 (10%) partial responses, 12 (60%) stable disease and 6 (30%) progressions were observed. Partial responses were maintained for 3 and 4 months respectively; stable disease had a median duration of 4 months. The overall median survival after progression was 7 months. From our results sequential high-dose methotrexate and 5-fluorouracil cannot be recommended as second-line chemotherapy in advanced colorectal cancer.

Adult↗
PubMed1990

Partial response of metastatic hepatocellular carcinoma after treatment with thymostimulin.

We describe a case of partial regression of metastatic hepatocellular carcinoma after treatment with thymostimulin. The patient, a 58-year-old man, received no specific therapy for his tumor, but only a thymus extract ("thymostimulin"). At follow-up 6 months later the patient showed clinical improvement, reduction of alpha-fetoprotein level an liver lesions, and a complete regression of lung metastases. The patient died of progression of the disease with 2-year overall survival.

Adjuvants, Immunologic↗
PubMedDate not supplied

Salvage chemotherapy for non Hodgkin's lymphoma of unfavourable histology with a combination of CCNU and vinblastine.

Twenty patients with relapsed or refractory, intermediate or high grade non Hodgkin's lymphoma were treated with a combination of CCNU and vinblastine. Complete responses occurred in four patients (20 per cent), partial responses in eight (40 per cent), for an overall response rate of 60 per cent. The regimen was more effective in patients with high grade lymphoma, absence of constitutional symptoms, better response to prior treatment. Duration of response was 4, 8, 16, 30 months for complete responders; 2, 2, 6, 6, 6, 8, 9, 14 months for partial responders. This combination regimen seems at least as effective as most of other regimens utilized in salvage treatment of non Hodgkin's lymphomas, with a very acceptable toxicity.

Adult↗
PubMedDate not supplied

CAVBP/DEP alternating chemotherapy for the treatment of intermediate and high grade non Hodgkin's lymphoma: final results of a pilot study.

Between May 1984 and September 1986, 40 patients with intermediate or high grade non Hodgkin's lymphoma were treated with a novel protocol, which alternated a conventional regimen consisting of cyclophosphamide, doxorubicin, vincristine, bleomycin, and prednisone (CAVBP) with a second chemotherapy regimen, including two drugs with newly discovered activity against lymphomas, such as cis-platin, etoposide, and prednisone (DEP). Twenty-one patients (52.5 per cent) achieved a complete response, 11 patients (27.5 per cent) had a partial response. Eight of the 21 complete responders (38 per cent) relapsed 5 to 24 months after completion of treatment. With a median follow-up of over 40 months, 22 patients are alive, six with disease and three in a second complete response after salvage chemotherapy. Factors negatively associated with response included 'B' symptoms, advanced stage of disease, bulky tumour, poor performance status, number of extranodal sites of disease. 'B' symptoms, bulky tumour, and poor performance status were also negatively associated with survival. Toxicity was modest, with no treatment-related deaths and only six cases of severe leukopenia. The results of this pilot study do not justify comparison of CAVBP/DEP with more efficacious regimens in prospective, randomized trials.

Adult↗