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Biomedical subjects

R Sorio

Publications and source records attributed to R Sorio.

67 records · Page 4Linked to original sources

HTLV-III infection among 315 intravenous drug abusers: seroepidemiological, clinical, and pathological findings.

Seroepidemiological, clinical, immunological, and pathological features were studied in 315 intravenous drug abusers (IVDA) seen in five centers for drug addicts' assistance in the Friuli Venezia-Giulia region of Italy, close to the borders of Austria and Yugoslavia. No case of AIDS has been observed. Sixty-five (21%) were affected by persistent generalized lymphadenopathy (PGL). HTLV-III seropositivity was noted in 86 (27%) of the overall 315 IVDA, in 50 (77%) of 65 patients with PGL, and in 1 (0.5%) of 205 blood donors tested as a control group. Patients with PGL had a significantly lower OKT4/OKT8 ratio than the rest of the IVDA population and controls. Systemic symptoms were present in 52% of the patients with PGL, the most frequent symptoms being fatigue and night sweats. In 20 patients with PGL, DR typing revealed a significant increase in DR-5 frequency and a significant decrease of DR-2 frequency. The predominant histological features in the lymph nodes taken from 25 patients consisted of an exuberant follicular hyperplasia, capillary vessel proliferation, and plasmacytosis. Nineteen (22%) females reporting occasional prostitution were compared to 10 non-IVDA female prostitutes and concomitantly evaluated. HTLV-III seropositivity was noted in 11 (58%) of 19 IVDA female prostitutes and in none of the 10 non-IVDA prostitutes. Thirty-five couples composed of both IVDA were compared to 24 couples composed of an IVDA and a non-IVDA. Among the 24 couples of whom one or both partners were seropositive, concordance in HTLV-III seropositivity was present in 5/11 (45%) couples composed of both IVDA, and in only 1/13 (8%) couples composed of an IVDA and a non-IVDA. This suggests that the sharing of contaminated needles, universally practiced by our IVDA population, plays a more important role in the transmission of HTLV-III than sexual contact.

AIDS-Related Complex↗

Phase II studies of 4'-iodo-4'-deoxydoxorubicin in advanced non-small cell lung, colon and breast cancers.

The new anthracycline analogue, 4'-iodo-4'-deoxydoxorubicin (I-DOX), was administered at 70 mg/m2 as first chemotherapy in 61 patients with advanced NSCL (19), colon (20) and breast cancers (22). Treatment was repeated every 3 weeks; the dose was decreased to 60 mg/m2 (19% of the cycles) or increased to 80 mg/m2 (17% of the cycles) according to the granulocyte count nadir. Partial responses were observed in 6% of the patients with NSCL, in 5.5% of those with colon and in 10% of those with breast cancers. The main toxicity was a selective granulocytopenia characterized by a duration of about 1 week, and a high inter-patient variability. Non-haematological toxicities were mild. The negative results obtained in breast cancer might be related to the dose administered. Further studies in this tumour type should be performed with a more aggressive schedule.

Adult↗

Interactions of antineoplastic chemotherapy with zidovudine pharmacokinetics in patients with HIV-related neoplasms.

To evaluate the perturbations in zidovudine (ZDV) pharmacokinetics as a consequence of antineoplastic chemotherapeutic treatments, we performed a prospective crossover study in 13 HIV-infected patients with cancer. The subjects received 2-day regimens of ZDV (250 mg x 2/day). On the first day ZDV was administered alone, whereas on the second day it was combined with antitumor chemotherapies specific for the histological type (ZDV + chemotherapy). Blood sample and urine collections were performed over a 12-hour period following oral administration of the antiretroviral agent. ZDV was measured with high-performance liquid chromatography. Pharmacokinetic parameters of ZDV were calculated by a noncompartmental model. The mean ZDV area under curve (AUC) was not significantly different in the patients treated with ZDV alone and ZDV + chemotherapy. Comparison of plasma elimination half-life (t((1/2))), apparent systemic clearance (CL/F), and apparent volume of distribution (Vd/F) of ZDV did not show any significant difference before and after chemotherapy. Conversely, some significant differences were observed for both mean peak concentration (C(max)) of ZDV and the corresponding time (T(max)). There was a 57% reduction in C(max) (p<0.05) and a 66% increase in T(max) (p<0.05) after chemotherapy compared with treatment with ZDV alone. No differences were observed in the urinary excretion of ZDV and ZDV glucuronide and urinary metabolic ratio, as a consequence of antineoplastic treatment. In conclusion, this study demonstrates that some minor perturbations in ZDV pharmacokinetics (i.e. C(max) and T(max)) derived from antineoplastic chemotherapy. Based on the observation that antineoplastic chemotherapy had no significant effect on plasma ZDV concentration expressed as AUC, the observed pharmacokinetic interaction would not warrant by itself a change in the ZDV dosage during chemotherapy.

Adolescent↗

Pentostatin (2'-deoxycoformycin, dCF) in patients with low-grade (B-T-cell) and intermediate- and high-grade (T-cell) malignant lymphomas: phase II study of the EORTC Early Clinical Trials Group.

Thirty-seven eligible patients with advanced non-Hodgkin's lymphoma of low-grade, T-cell intermediate- and high-grade histology were treated with pentostatin (2'-deoxycoformycin, dCF) 4mg/m2 i.v. weekly for 3 weeks and then every 14 days to be followed after 3 doses by the same dosage every 4 weeks until maximum response or progression. Only patients with no more than two chemotherapy regimens were entered in this trial. All patients had measurable disease, performance status of 1,0 and 2 and adequate bone marrow, renal and liver function. Five of 37 eligible patients experienced a partial response of 8 months' median duration (range 7-12). The response rate was 17% in low-grade, 8% in T-cell intermediate- and high-grade and 14% in cutaneous T cell lymphoma. The only eligible patient with Hodgkin's disease underwent progression while on treatment. One case presented with grade 3 leukopenia and another one died of septicaemia, possibly treatment-related. Elevated but reversible creatinine levels were observed in 13% of patients and conjunctivitis in 7%. The toxicity of dCF at this low-dose schedule was acceptable, but the therapeutic activity in pretreated patients with low-grade, T-cell intermediate- and high-grade and cutaneous T-cell lymphomas was limited.

Adult↗

Occult small cell lung cancer associated with paraneoplastic neurologic syndrome: case report.

Cancer is often associated with paraneoplastic syndromes, which may be misinterpreted. We report a case of a patient with occult small cell lung cancer that was initially compounded by clinical features of a paraneoplastic neurologic syndrome. The presence of antineuronal antibodies and positron emission tomography scan guided the search for the underlying tumor. Following chemo-radiotherapy the patient showed no evidence of disease for the next 18 months, whereas only a slight improvement in the neurologic disorders was observed. The course of the small cell lung cancer was very indolent and the paraneoplastic neurologic syndrome did not worsen with the use of cisplatin.

Ataxia↗

Gastric cancer with bone marrow invasion at presentation: case-report and review of the literature.

A case of extensive bone marrow infiltration due to gastric cancer is reported. A 65-year old man with an acute episode of anemia (Hb 4.1 mg/dl) and dyspnea was admitted to the Medical Department of a general hospital. Bone marrow biopsy showed extensive paratrabecular infiltration of a poorly differentiated adenocarcinoma of gastric origin. The primary tumor in the stomach was confirmed, and the patient was referred to our Institute and treated with combination chemotherapy (FAMTX) for 6 cycles. Due to the disappearance of bone marrow infiltration, the patient was considered for curative resection of the primary gastric cancer. After 27 months the patient is alive and in clinical complete remission.

Adenocarcinoma↗

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↗

Pharmacology of chronic oral daily administration of idarubicin.

Idarubicin (4-demethoxydaunorubicin) (IDA) is a daunorubicin analogue with substantial activity in hematologic malignancies and solid tumors. Among several reasons, IDA is of interest because of its main metabolite derivative, the C-13 alcohol analogue, idarubicinol (IDOL). Previous studies have suggested that IDOL, unlike other anthracycline metabolic derivatives, possesses a striking growth-inhibitory activity in tumor cell lines. This suggests that IDOL, like IDA could be useful in circumventing MDR. IDA is bioavailable in an oral dosage form. After oral administration of IDA to the patients, the concentration of IDOL quickly exceeds that of IDA and is retained in the plasma for a longer period. Hence, administration of IDA to cancer patients results ina much greater overall exposure of the tumor to IDOL than to the parent compound. At the Oncology Center (CRO) in Aviano we performed a dose-finding and pharmacokinetic (PK) study of chronic daily oral IDA with intrapatient escalation in patients with metastatic breast cancer (MBC). All the patients were pretreated with anthracyclines (the cumulative dose was 530 mg and 264 mg, respectively, for epirubicin and (DOX) and had at admittance a PS < or = 2 and a left ventricular ejection fraction > 50%. IDA (1 mg capsules) was administered orally twice a day for 21 days every two weeks. Treatment was continued at escalating doses until progression or intolerance. Twenty-five patients were enrolled. MTD has not yet been reached and clinical results are reported in Table 1. Treatment was well-tolerated in all but one patient (300 ANC at day 28). Three patients had tox G3 ANC for more than three weeks after 3, 6, and 7 mg doses, respectively. Two of them stopped chemotherapy after 1 cycle and 1 patient stopped after 2 cycles (6 mg doses). Despite previous treatments with anthracyclines (the mean cumulative dose before entering the study was 530 and 264 mg, respectively, for epirubicin and DOX) no cardiotoxicity due to IDA treatment was observed. This trial demonstrates the feasibility of chronic daily IDA administration. At the dosage reported, treatment was generally well tolerated. The PK findings (high IDOL concentrations) and the unexpected G4 myelotoxicity in patients with the highest IDOL plasma concentrations suggest that IDOL is clinically relevant.

Administration, Oral↗