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Biomedical subjects

C Sessa

Publications and source records attributed to C Sessa.

At least 127 records · Page 7Linked to original sources
PubMed1993

New cytostatic drugs in ovarian cancer.

BACKGROUND: Many ovarian cancer patients will after treatment of the recurrence with cisplatin based therapy enter phase I or II studies with new drugs. Lately, some new agents have shown activity. MATERIALS AND METHODS: The review is based on phase II studies mainly and focuses on paclitaxel (taxol). RESULTS: A Canadian/European study of high (175 mg/m2) versus low dose (135 mg/m2), and short (3 hours) versus long (24 hours) infusion confirms the reported activity of paclitaxel in previously treated patients. The preliminary overall response rate in 286 evaluable patients is 18.5%. A dose effect exists regarding neuropathy and neutropenia, and a longer infusion duration results in a higher frequency of grade 4 neutropenia. In a phase III study comparing cisplatin 75 mg/m2 plus cyclophosphamide (750 mg/m2) or plus paclitaxel 135 mg/m2 over 24 hours, the paclitaxel-based combination gave a superior response rate (54% versus 33%) and statistically significant longer progression-free interval. The semisynthetic docetaxel (taxotere) gives an overall response rate of 32% (95% confidence interval 23%-43%). Skin toxicity and edema are dose-limiting factors. Gemcitabine has also shown activity in platinum-resistant patients with an overall response rate of 23% (95% CI 10%-40%). CONCLUSIONS: The role of new drugs in first-line therapy remains to be seen. Further development of experimental work for screening and evaluation of new agents is needed.

Antimetabolites, Antineoplastic↗
PubMed1993

Childhood acute promyelocytic leukemia in Nicaragua.

BACKGROUND: The pediatric hematology-oncology service of the Managua 'La Mascota' Children's Hospital in Nicaragua began its activities in 1988. We report on unusual high incidence of acute promyelocytic leukemia (APL) observed in Nicaragua in the last three years. PATIENTS AND METHODS: From 1990 to 1992, 17 of 110 children with acute leukemia were diagnosed as having acute non-lymphoblastic leukemia (AnLL). The diagnosis was performed according to the FAB criteria. In two cases DNA was recovered for molecular analysis of the t(15; 17). RESULTS: Ten of 17 cases of AnLL were classified as APL. PML and RAR alpha gene rearrangements were observed in the two cases where molecular analysis was performed. Nine children received chemotherapy; one was treated with all-trans-retinoic acid (ATRA), achieving complete remission. Eight children who received chemotherapy died early of hemorrhage and/or sepsis. DISCUSSION: In Nicaragua, APL may be much more common than is generally observed elsewhere. In recent years initial treatment of APL with ATRA has proved to reduce the incidence of early hemorrhagic deaths, and complete remissions can be achieved without marrow aplasia and thus prevent infectious complications. From that perspective APL might become a curable disease, also in developing countries where the treatment of AnLL is not usually affordable.

Adolescent↗
PubMed1993

Low-dose oral etoposide in epithelial cancer of the ovary.

AIMS: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of low-dose oral etoposide (E) in patients (pts) with epithelial cancer of the ovary previously treated with cisplatin. PATIENTS AND METHODS: Eighteen pts receiving 50 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of bioavailability and weekly 24-hour drug concentrations. RESULTS: Among 17 evaluable pts, 1 partial remission of 9 months. Dose-limiting neutropenia of high inter-patient variability. Mean bioavailability value of 75%, ranging from 44% to 100%. No correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC during the first cycle. CONCLUSIONS: Low-dose oral E is ineffective as salvage treatment in epithelial cancer of the ovary. The large variability of neutropenia requires a careful hematological monitoring to avoid severe myelosuppression.

Administration, Oral↗
PubMed1993

Chronic oral etoposide in small-cell lung cancer: clinical and pharmacokinetic results.

AIMS: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of chronic oral etoposide (E) in patients (pts) with small-cell lung cancer (SCLC) previously untreated with chemotherapy. PATIENTS AND METHODS: Twenty-seven (14 extensive-, 13 limited-stage) pts receiving 100 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of weekly 24-hour drug concentrations. RESULTS: Among 25 evaluable pts, 60% (95% CI: 39%-79%) overall response, 144 and 217 days of median PFS and survival. Dose-limiting non-cumulative neutropenia of high interpatient variability. Linear reduction (30% per week) of absolute neutrophil counts (ANC) up to the 3rd week, recovering the following week. Risk factors for neutropenia (age, PS, serum creatinine and albumin) not identified. High inter-patient variability of 24-hour E plasma levels. A weak correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC, but higher relative decrease of ANC in pts with 24-hour E plasma levels of > 0.32 microgram/ml. CONCLUSIONS: Chronic oral E is effective in SCLC pts previously untreated with chemotherapy. Careful hematological monitoring is essential to avoid severe myelosuppression. The degree of neutropenia might be related to the maintenance of a critical drug concentration level for a critical period of time.

Administration, Oral↗
PubMed1992

Activity of aphidicolin glycinate alone or in combination with cisplatin in a murine ovarian tumor resistant to cisplatin.

Aphidicolin, a reversible inhibitor of DNA polymerase alpha and delta, has recently been reported to reverse the resistance to cisplatin (DDP) of an ovarian cancer cell line. We investigated the pharmacokinetics of aphidicolin in mice and examined its activity either alone or in combination with DDP in the DDP-sensitive M5076 (M5) murine reticular cell sarcoma as well as in a DDP-resistant subline (M5/DDP). The drug was cleared from plasma very rapidly (clearance, 41.6 ml min-1 kg-1), showing a half-life of 15 min. Aphidicolin concentrations in the tumor were approximately 50% of those found in plasma at steady state. Using several dose schedules and continuous infusions we failed to detect significant antitumor activity for aphidicolin glycinate. Potentiation of the activity of DDP by aphidicolin glycinate was moderate in mice bearing M5 tumor as well as in those bearing M5/DDP tumor. These data do not support the possible clinical use of aphidicolin in combination with DDP. However, further studies should be carried out in different tumor models before this possibility is conclusively ruled out.

Animals↗
PubMed1991

Phase I and clinical pharmacological evaluation of aphidicolin glycinate.

The toxicity profile and the pharmacokinetics of aphidicolin glycinate, a water-soluble analogue of aphidicolin, have been evaluated in two consecutive phase I clinical studies. In the first study, aphidicolin glycinate was given by 1-hour infusion for 5 consecutive days, every 3 weeks (daily x 5 study); in the second study, which was planned on the basis of the pharmacokinetic information obtained in the previous study, the drug was given by 24-hour continuous infusion. Treatment was repeated every 3 weeks. In the daily x 5 study, the daily dose was escalated from 12 mg/m2 to the maximum tolerated dose of 2250 mg/m2. Local toxicity was dose limiting. Elimination half-life was 2 +/- 0.2 hours (mean +/- SE) with aphidicolin being undetectable 6-8 hours after the end of the infusion. In the 24-hour continuous-infusion study, the dose was escalated from 435 mg/m2 to the maximum tolerated dose of 4500 mg/m2. Local toxicity was dose limiting, while other toxic effects were absent. The experimentally determined concentrations at the steady state were in agreement with those predicted on the basis of the available pharmacokinetic data. The targeted concentration at the steady state of 3 micrograms/mL was achieved at doses greater than or equal to 3000 mg/m2. Twenty-four-hour continuous infusion is the recommended schedule for clinical evaluations of aphidicolin glycinate as the synchronizing agent or in combination with cisplatin.

Adult↗
PubMed1991

Phase I study of the combination of monthly carboplatin and weekly cisplatin.

Two cycles of the combination of carboplatin (C), given every 4 weeks with weekly doses of cisplatin (P), were administered on an outpatient basis to 28 previously untreated patients. One cycle consisted of one dose of C and 4 doses of P. The toxicity of 250 mg/m2 of C, combined with escalating doses of P (20, 30, 35, 40 mg/m2) was evaluated first. Thrombocytopenia was dose-limiting and cumulative. At the dose level of 40 mg/m2 of P, the median Pt nadirs during the first and second cycles were 190 (range: 44 to 232) x 10(3)/microL and 90 (range: 15 to 165) x 10(3)/microL, respectively. The median delivered dose intensity (DI) of P was 40 mg/m2/wk in the first cycle and 40 mg/m2/wk in the second cycle. In the second part of the study, 40 mg/m2 of P were combined with a C dose adapted to individual renal function according to the formula dose (mg) = AUC x (GFR + 25) where AUC = 4.5 mg/mL/min. The administration of doses of C ranging from 219 to 493 mg/m2 was associated with a more severe and more variable thrombocytopenia, more frequent P delays and decrease of the median delivered DI of P (first cycle: 33 mg/m2/wk; second cycle: 32 mg/m2/wk). At all dose levels, leukopenia was mild to moderate, and neurotoxicity and severe GI toxicity were absent. No significant reductions of the creatinine clearance values were observed. All patients treated at 40 mg/m2 of P suffered from cumulative subjective toxicity during the second month of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

A gas chromatographic mass spectrometric assay for the determination of aphidicolin in plasma of cancer patients.

A gas chromatographic-mass spectrometric (GC-MS) method is described for the determination of the novel anticancer agent aphidicolin in plasma. The extraction was carried out in a solvent mixture of hexane:isopropanol (10:1) and the external standard aphidicolane was added after evaporation of the organic phase. The residue was then redissolved in a derivatizing mixture containing bis(trimethylsilyl)trifluoracetamide as sililating agent, pyridine, and trimethylchlorosilane, and allowed to react at 80 degrees C for 2 h. After GC separation of the derivatized samples, selected ion recording analysis was done, monitoring the ions at mass 523.3 and 448.3 for aphidicolin and aphidicolane, respectively. The mean recovery +/- SD of aphidicolin from plasma was 73.5 +/- 11.6% in the range from 5 to 800 ng. This method was applied to determine aphidicolin plasma levels in three cancer patients in Phase I clinical trials of aphidicolin-17-glycinate administered as a 1-h iv infusion. Two patients received dose of 290 mg/m2 and the third received 435 mg/m2. Aphidicolin plasma levels at the end of infusion were very low, and the drug rapidly disappeared from plasma with a terminal (beta) half-life of 2 h.

Adult↗
PubMed1989

A phase II study of spirogermanium in patients with advanced malignant lymphoma.

Spirogermanium was given as a 90 minute infusion to 47 eligible patients with refractory Hodgkin's (9 patients) or non-Hodgkin's lymphoma (38 patients). The schedule was 80 mg/m2 three times a week for the first two weeks and 100 mg/m2, 3 times a week, for the two subsequent weeks. In case of response or stable disease, the treatment was continued with biweekly infusions of 100 mg/m2 until tumor progression. In 64% of cases, three or more combinations had been previously administered; 66% of patients presented an extra-lymphatic spread of disease. Two patients with Hodgkin's disease showed a partial response of 11 and 23 weeks and two patients with non-Hodgkin's lymphoma achieved a complete response of 12 and 24 weeks. Overall, 14 patients showed a tumor progression within the first month of treatment. The main toxicity was neurological, with dizziness and lethargy during the infusion in 50% of cases. Hematologic toxicity was almost absent. Spirogermanium is ineffective in heavily pretreated patients with non-Hodgkin's lymphoma. The confirmed lack of activity in patients with refractory malignant lymphoma and the need of repeated and prolonged infusions definitely discourage the clinical use of the drug.

Adult↗
PubMed1988

Phase II study of intravenous menogaril in patients with advanced breast cancer.

Menogaril was administered to 40 patients with advanced breast cancer who had not received anthracycline drugs previously. The drug was given iv as a 2-hour infusion, repeated every 4 weeks, at doses of 200 mg/m2 and 160 mg/m2 in good-risk and poor-risk patients. The overall response rate was 22% in patients with no prior chemotherapy and 10% in patients previously exposed to chemotherapy. Leukopenia was generally moderate and predictable. Phlebitis and erythema along the vein injected occurred in 34% and 17% of the cases, respectively. Menogaril is an active drug used in the treatment of patients with advanced breast cancer who have not had prior systemic therapy.

Adult↗
PubMed1988

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Abdomen↗