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R Canetta

Publications and source records attributed to R Canetta.

At least 19 recordsLinked to original sources
PubMed1995

Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.

PURPOSE: To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS: Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS: In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION: Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.

Adult↗
PubMed1992

Effects of therapy with didanosine on hematologic parameters in patients with advanced human immunodeficiency virus disease.

Myelosuppression is associated with human immunodeficiency virus (HIV) infection and may also be produced by agents used for the treatment of the disease or the treatment of its complications. Didanosine (ddl; 2',3'-dideoxyinosine) is a newer purine nucleoside that has recently become available for therapy for HIV infection. The effects of didanosine on peripheral blood counts have been retrospectively evaluated in the first 170 patients treated with this new agent in four phase I trials. Patients treated with didanosine showed statistically significant improvements in hemoglobin levels, white cell counts, and granulocyte and platelet numbers as compared with baseline values. These changes were seen with or without prior therapy with zidovudine, were somewhat more pronounced at higher doses of didanosine, and persisted for up to 1 year. Reported adverse events included peripheral neuropathy, diarrhea, and most notably, pancreatitis. It is concluded that, while some toxic side effects occur, didanosine therapy in HIV infection is associated with an amelioration of HIV-induced myelosuppression.

AIDS-Related Complex↗
PubMed1992

A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

Adult↗
PubMed1991

Phase I study of 2'-3'-dideoxyinosine administered orally twice daily to patients with AIDS or AIDS-related complex and hematologic intolerance to zidovudine.

PURPOSE: To evaluate the safety and hematologic tolerance of 2'-3'-dideoxyinosine (didanosine, ddI) in subjects with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and prior hematologic intolerance to zidovudine. PATIENTS AND METHODS: A Phase I trial with two dose groups at a single-center, university-affiliated hospital ambulatory care center. Of 30 subjects enrolled, 21 had AIDS and nine had AIDS-related complex. All had CD4 lymphocyte counts less than 0.2 x 10(9)/L at entry. Didanosine was administered orally twice daily at a total daily dose of 750 mg or 1,500 mg for 12 weeks. Subjects who completed the 12-week study continued to receive ddI at the lower dose. All subjects were monitored for toxicity. Virologic and immunologic response markers were also measured. RESULTS: For the group as a whole, there was no significant decrease in mean hemoglobin level or leukocyte or platelet counts. The dose-limiting toxicity was peripheral neuropathy. Other significant toxicities included pancreatitis and hypocalcemia. Uric acid elevations were common but were without clinical consequence. A sustained decrease in serum p24 antigen of at least 50% was noted in 42% of subjects who were p24 antigen-positive at entry. The mean CD4 lymphocyte count showed an initial increase that was not sustained over the 12-week study. All subjects remained anergic to skin testing. CONCLUSIONS: Didanosine is well tolerated hematologically in some patients with prior significant hematologic intolerance to zidovudine. The toxicity profile for ddI differs from that of zidovudine and includes peripheral neuropathy and pancreatitis. Changes in CD4 lymphocyte number and HIV p24 antigen levels in some patients suggest antiviral activity of ddI in this population.

AIDS-Related Complex↗
PubMed1990

Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.

From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.

Adenocarcinoma↗
PubMed1990

Overview of hormonal therapy in advanced breast cancer.

Hormonal therapy of breast cancer is widely used and effective. Although never curative in advanced disease, significant palliation and durable remissions can be obtained with a wide variety of hormonal manipulations. Historically, surgical ablation was used to reduce endogenous hormone levels, but this invasive procedure has been largely supplanted by drugs that reduce hormone secretion or block steroid hormone activity. A number of such antagonists are available, with tamoxifen probably the most widely used. Response can also be achieved with hormone agonists. Estrogens and androgens or their congeners have about the same level of activity as surgical ablation or drug antagonists (20% to 30% overall response rate). The progestins, another class of agonists, are also effective in the palliation of advanced breast cancer. Megestrol acetate, in part because of its oral formulation, is probably the most commonly used progestational drug for the treatment of breast cancer. Reports of 16 trials involving 1,342 patients show a response rate of 26% in patients with advanced breast cancer treated with megestrol acetate. The drug has proved active in a small number of male patients and, in randomized trials, it has been shown to be comparable with tamoxifen in efficacy (30% response for megestrol acetate v 35% for tamoxifen). Studies are currently under way to evaluate the possibility that high doses of megestrol acetate may increase response rates, and to determine whether weight gain, a well-described effect of this drug, may prove beneficial in cancer treatment.

Breast Neoplasms↗
PubMed1990

Carboplatin in the first-line chemotherapy of ovarian cancer.

When used as first-line treatment for advanced ovarian cancer in phase III trials, single-agent carboplatin has produced clinical complete response rates comparable with or exceeding those of single-agent cisplatin. Phase I/II trials of combination chemotherapy have yielded overall objective response rates of 44% to 75% when carboplatin was combined with either cyclophosphamide or chlorambucil. In randomized phase III trials of carboplatin combination chemotherapy, response rates similar to those of cisplatin combinations have been achieved but with greatly reduced toxicities. The data from these phase I, II, and III trials show that carboplatin is as active as cisplatin in patients with advanced ovarian cancer and is associated with a significantly lower incidence and is associated with a significantly lower incidence of emesis, ototoxicity, peripheral neuropathy, and renal dysfunction. Thus, carboplatin should be considered the platinum compound of choice in the firstline treatment of advanced ovarian cancer.

Antineoplastic Agents↗
PubMed1989

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.

Carboplatin (CBDCA) is a second-generation cisplatin analog that has shown activity in early clinical trials. Its spectrum of toxicity is quantitatively and qualitatively different from that of the parent compound. Between November 1984 and September 1986 we conducted a phase II trial of CBDCA in 46 women with epithelial ovarian cancer. All patients had undergone at least one prior chemotherapy regimen; 41 (89%) had previously received cisplatin (mean cumulative dose, 540 mg/m2). The CBDCA dose was based on renal function and was injected i.v. once every 4 weeks. Patients were stratified on the basis of baseline creatinine clearance: those with a baseline creatinine clearance of greater than or equal to 60 ml/min received 400 mg/m2 CBDCA; those with a creatinine clearance between 30 and 60 ml/min received an initial dose calculated according to a previously published formula that corrected for renal insufficiency and projected nadir platelet counts of 75,000/mm3. Of 41 evaluable patients, 6 (15%) had an objective response [2 complete responses (CRs); 4 partial responses (PRs)]; 5 of the 6 responders had previously responded to cisplatin treatment. No responses were observed in 12 patients who had not responded to prior cisplatin therapy. Significant hematologic toxicity was seen. Of 18 patients with a creatinine clearance of greater than or equal to 60 ml/min (dose, 400 mg/m2), 6 had nadir platelet counts of less than 25,000/mm3, 4 with symptomatic bleeding. Of the 21 evaluable patients for whom the dose-modification formula was applied, 10 had nadir platelet counts of less than 75,000/mm3; 5 had counts of less than 50,000/mm3. CBDCA has activity even in patients who have previously undergone extensive cisplatin therapy; however, its toxicity is variable and thrombocytopenia is dose-limiting. We did not confirm the ability of the above-mentioned formula to calculate the CBDCA dose and accurately predict the nadir platelet count for all patients. Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients.

Acute Disease↗
PubMed1987

Non-Hodgkin's lymphomas in the elderly: prospective studies with specifically devised chemotherapy regimens in 66 patients.

The results of 2 consecutive and prospective trials with specifically devised chemotherapy regimens in elderly patients (pts) with non-Hodgkin's lymphoma (NHL) are reported. Between August 1979 and September 1984, 66 pts aged 70 or older (median 75 years) with NHL entered 2 consecutive trials, the former with single agent teniposide 100 mg/m2 i.v. weekly (41 pts), the latter with etoposide and prednimustine (E + P), 100 mg/m p.o. for 5 days every 21 days (25 pts). Forty-five pts were previously untreated, 21 previously treated. Forty-seven pts were of the intermediate and high grade groups according to the Working Formulation; 19 pts were of the low grade; 57 pts were stages III and IV, 9 pts were stages I and II. The median performance status was 70 (range 30-100). The objective response rate in the 66 evaluable pts is 53% with 38% CR; the 3-year overall, disease-free and CR survivals are 21, 12 and 40% respectively. The objective response rate in the 45 previously untreated pts is 58% with 42% CR; the 3-year overall, disease-free and CR survivals are 24, 16 and 58% respectively. The overall toxicity was mild. Severe toxicity (grade III and IV according to WHO criteria) was observed only in 16/498 courses (3.2%), with 1 toxic death (grade IV leucopenia). We experienced the usefulness of a properly orientated clinical approach to elderly pts with NHL. We suggest that a combination regimen like E + P, suitable for oral administration, may be safely employed in a large fraction of pts with NHL.

Aged↗
PubMed1987

Clinical status of carboplatin.

Carboplatin, a cisplatin derivative, shows promise of being an effective weapon against ovarian, cervical, and small-cell lung cancer, as well as epidermoid cancer of the head and neck, with fewer toxic effects than cisplatin. It has successfully completed phase III investigation and clinical trials continue.

Animals↗
PubMed1985

Carboplatin: the clinical spectrum to date.

The existing literature data base on carboplatin updated to June, 1985 has been reviewed. The compound seems to retain the same spectrum of activity as cisplatin, and a definite set of efficacy data is available for ovarian cancer of epithelial origin, small cell carcinoma of the lung and epidermoid carcinoma of the head and neck. A yet unpublished toxicity data base on carboplatin suggests that the compound has an improved therapeutic index over the parent compound, cisplatin, and that it does not seem inferior to another platinum coordination compound currently in clinical trials, iproplatin.

Antineoplastic Agents↗
PubMed1984

A clinicopathologic study in advanced non-Hodgkin's lymphomas treated with sequential non-cross-resistant regimens: comparison of the working formulation with the Rappaport and Kiel classifications.

One-hundred and ninety-four adult patients with histologically proven stage III and IV non-Hodgkin's lymphomas, treated with CVP (cyclophosphamide, vincristine and prednisone) alternated with ABP (adriamycin, bleomycin and prednisone), were analyzed to test the validity of the clinicoprognostic correlation offered by the working formulation in comparison with the Rappaport and Kiel classifications. Actuarial overall survival at 5 yr showed a significant difference among the three prognostic subgroups of the working formulation (low grade, 53.3%; intermediate grade, 47.5%; high grade, 27.7%). Overall survival of favorable subgroups of the Rappaport and Kiel classifications was superior to that of unfavorable prognostic groups. The percentage of systemic symptoms and bulky disease increased in patients with low-grade compared to those with intermediate-grade and intermediate-to-high-grade malignancy. The achievement of complete remission was not related to any of the prognostic groups of the Working Formulation, and no difference could be detected within the various prognostic groups of the Rappaport and Kiel classifications. Within the diffuse histiocytic lymphomas of the Rappaport classification, two groups with a different prognostic outcome were evidenced by the working formulation (G, with an overall survival of 50%, and H, with an overall survival of 26.7% at 5 yr) and by the Kiel classification. The possibility of reporting results in the three different groups of the working formulation instead of two can be considered a step forward. Within the diffuse histiocytic histology, the working formulation allows separation, as does the Kiel classification, into two main different prognostic subgroups.

Adolescent↗
PubMed1984

Etoposide (VP-16-213) in malignant brain tumors: a phase II study.

Twenty-two consecutive patients with recurrent malignant brain tumors after radiation therapy and systemic combination chemotherapy with BCNU and vincristine, four of whom were not evaluable due to early death, were treated with etoposide (VP-16-213) (50-100 mg/m2 for five days every three weeks). Response, defined as improvement in both clinical examination and computed tomography scan in absence of glucocorticoids dosage increase, was observed in three (17%) of 18 evaluable patients, lasting greater than 21, seven, and two months, respectively. Six additional patients had stable disease for greater than 10, seven, four, four, three, and two months: all of them had improvement of clinical symptoms but no variation in their scans. Overall median survival from the start of VP-16-213 was 4.5 months (range, 1-23 + months), whereas patients with response or stable disease had a median survival of eight months. Overall, treatment was well tolerated. In 10 patients concomitant plasma and cerebrospinal fluid samples were evaluated with a high-performance liquid chromatographic method for drug assay. The concentration of VP-16-213 in cerebrospinal fluid was less than 1% that found in plasma, even in the two patients with response. The activity of etoposide in patients with malignant, lomustine-vincristine-resistant brain tumors suggests an interesting potential use for this drug.

Adolescent↗
PubMed1983

Megestrol acetate.

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Adenocarcinoma↗