PubMed Health⌕ Search

Biomedical subjects

A Romanini

Publications and source records attributed to A Romanini.

At least 19 recordsLinked to original sources
PubMed2005

Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome.

BACKGROUND: This study was designed to determine the debated prognostic significance of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity in melanoma patients' sentinel lymph node (SLN) negative by conventional histopathology (PATH). PATIENTS AND METHODS: Patients with primary stage I-II cutaneous melanoma underwent radioguided sentinel lymphadenectomy. Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin staining and immunohistochemistry. Tyr and MART-1 expression in the SLNs were correlated with PATH assay results, standard prognostic factors, time to progression and overall survival. RESULTS: Twenty-three of the 124 patients (18.5%) had positive SLNs by both PATH and RT-PCR (PATH+/PCR+). Sixteen patients (13%) were negative by PATH and positive by RT-PCR (PATH-/PCR+). Eighty-five patients (68.5%) had SLNs that were negative by both PATH and RT-PCR (PATH-/PCR-). At a median follow-up of 30 months, recurrence rates among the three cohorts were statistically different (PATH+/PCR+, 60%; PATH-/PCR+, 31%; PATH-/PCR-, 9.4%). Seven of 23 (30%) and two of 16 (12.5%) patients died in the PATH+/PCR+ and PATH-/PCR+ SLN groups, respectively, whereas no patient died in the PATH-/PCR- SLN group. CONCLUSIONS: RT-PCR is more sensitive than PATH to detect SLN metastases and it is a reliable predictor of disease relapse in stage I-II melanoma patients.

Adult↗
PubMed2003

First-line chemotherapy with epidoxorubicin, paclitaxel, and carboplatin for the treatment of advanced epithelial ovarian cancer patients.

OBJECTIVE: A combination of carboplatin (CBDCA) and paclitaxel (TAX) is the standard treatment in advanced ovarian cancer (AOC) patients. Epidoxorubicin (EDX) is an active treatment in AOC and exhibits nonoverlapping toxicities with CBDCA and TAX; moreover, when added to platinum-based chemotherapy, it improves long-term survival. We have therefore conducted a phase II study to evaluate the tolerability and antitumor activity of an EDX/TAX/CBDCA (ETC) triplet in AOC patients. METHODS: Patients with histologically confirmed suboptimal stage III-IV ovarian cancer who had not previously received cytotoxic drugs were treated with TAX (175 mg/m(2) in a 3-h iv infusion), CBDCA (AUC 6, Calvert formula), and EDX (75 mg/m(2) iv bolus) all given on day 1 every 28 days for a maximum of six courses on an outpatient basis. EDX dosage was chosen after a pilot phase I study. RESULTS: Fifty-five patients were registered, of whom 5 were determined ineligible bacause of age. Forty-two of the 50 are evaluable for response; 27 (64%) achieved a clinical complete response (CR) and 9 (21%) a partial response (PR) for a response rate of 86% (95% CI 71-94%). Thirty-three patients underwent a secondary debulking procedure after a median of 6 courses (range 2-6). Pathological CR and PR were observed in 9 (27.3%) and 21 (63.6%), respectively; among patients with persistent disease a successful cytoreduction (<1 cm) was obtained in 53.8% of patients. At a median follow up of 35.6 months (range 0-55.5) median progression-free survival is 19.5 months and median overall survival is 36 months. The most common adverse effects were G3-4 leukopenia and thrombocytopenia which occurred in 59 and 37% of patients, respectively. CONCLUSIONS: The ETC combination given according to the outlined doses and schedule is highly active in AOC patients with poor prognostic factors and deserves further study.

Adult↗
PubMed2003

Quality of life evaluation in a randomised trial of chemotherapy versus bio-chemotherapy in advanced melanoma patients.

This study analyses the health related quality of life (HRQOL) of advanced melanoma patients, in a randomised trial comparing bio-chemotherapy (bio-CT) versus chemotherapy (CT). The trial enrolled 178 patients and the median survival was not statistically different between the two arms. HRQOL was assessed at baseline and before each cycle of therapy, using the Rotterdam Symptom Checklist (RSCL) questionnaire completed with 140 patients. At baseline, overall quality of life and psychological distress scores were the most impaired, compared with the normal population. During treatment, the difference between the two arms in the changes from baseline was statistically significant (P=0.03) only in the overall quality of life score, with a decrease of 6.28 points in the bio-CT arm. The mean values decreased significantly in all domains in bio-CT arm, but only in activity level and physical symptom distress scores in the CT arm. Testing HRQOL variables and prognostic clinical factors in a Cox model, only the serum level of lactic dehydrogenase, baseline overall quality of life and the physical symptom distress scores remained significant independent prognostic factors for survival. A score of less than 75 points in the overall quality of life and in the physical symptom distress domains was associated with a Hazard Ratio (HR) of 2.31 (95% Confidence Interval (CI): 1.09-4.90) and 1.92 (95% CI: 1.10-3.36), respectively.

Adult↗
PubMed2003

Chemotherapy and bio-chemotherapy in patients with advanced melanoma: combination therapy with a nitrosourea.

The treatment of advanced melanoma is still disappointing. In a multicenter randomized clinical trial to compare a chemotherapy (CT) with or without low doses of IL-2 and IFN (Bio-CT), the participating centers chose whether or not to add a nitrosourea, carmustine (BCNU) to the therapy. The aim of the present paper is to report the clinical results of the patients (pts) treated in both arms with BCNU. One hundred and seventy-six pts with advanced melanoma were enrolled in the study from 27 centers and a total of 18 pts also received BCNU in 3 centers. No further changes to the protocol criteria were allowed. One patient refused the treatment. No complete responses were observed. Irrespectively of the treatment arm, 9/17 pts showed a partial response to therapy (53%) (5/9 in the CT and 4/8 in the BioCT arm). The most important adverse events observed were hematological: 12 pts presented grade 3 (6 pts) or grade 4 (6 pts) leukocytopenia and 9 pts had grade 4 thrombocytopenia, all of which resolved spontaneously. The addition of a nitrosourea to CT or Bio-CT appears to improve response rates compared to the same regimens without nitrosourea. Patient tolerability is acceptable. Further studies using this combination are warranted.

Adult↗
PubMed2001

Adjuvant chemotherapy in early stage uterine sarcomas: an open question.

Uterine sarcomas are aggressive gynecological cancers even at early stage of disease. The most common histological types are represented by leiomyosarcoma, endometrial stromal sarcoma, and carcinosarcoma. The mainstay of treatment of stage I-II disease is total hysterectomy with bilateral salpingo-oophorectomy. Adjuvant radiotherapy may decrease local recurrence rates without any significant impact on survival. Adjuvant chemotherapy is a logical approach, since distant recurrences are more frequent than local failures. The chemotherapy regimens commonly used in advanced uterine sarcomas are similar to the ones for advanced soft tissue sarcomas, with anthracyclines and ifosfamide as the most active drugs. However, carcinosarcomas respond better to cisplatin-based regimens. It is advisable to design international cooperative randomized trials with the aim of defining the role of adjuvant chemotherapy in the treatment of early stage uterine sarcomas.

Antineoplastic Agents↗
PubMed2000

Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest.

Intraperitoneal chemotherapy has a strong biological and pharmacological rationale in the treatment of ovarian cancer. From 1989 to 1996 the present study included 113 patients with FIGO stage II-IV ovarian cancer with residual disease less than 2 cm who were randomly allocated to receive 50 mg/m(2) intraperitoneal cisplatin (CDDP) plus 60 mg/m(2) intravenous epidoxorubicin (EPIDOX) and 600 mg/m(2) intravenous cyclophosphamide (CTX) (ipPEC arm) or 50 mg/m(2) intravenous CDDP plus 60 mg/m(2) intravenous EPIDOX and 600 mg/m(2) intravenous CTX (ivPEC arm). Chemotherapy was repeated every 4 weeks for six cycles. Treatment protocol was changed in 22 patients, 2 from the iv arm (who received single-agent carboplatin) and 20 from the ip arm (who were crossed to systemic chemotherapy, ivPEC, or single-agent carboplatin). At the end of chemotherapy, a second-look was performed in 33 of the 54 patients from the ip arm and in 34 of the 57 patients from the systemic arm. The pathologic complete response rate was 41% of all entered patients and 69% of patients submitted to second-look. No significant difference in pathologic response rate as well as in hematologic and nonhematologic toxicities was seen between the two arms. Up to September 1998, 72 patients showed a disease recurrence (33 treated with ipPEC and 39 treated with ivPEC), 55 died (22 ipPEC and 30 ivPEC), and 10 were lost to follow-up (6 ipPEC and 4 ivPEC). Median progression-free survival was 42 and 25 months for ipPEC and ivPEC, respectively (p = 0.13). Median overall survival was 67 and 51 months for ipPEC and ivPEC, respectively (p = 0.14). In conclusion, besides confirming that intraperitoneal chemotherapy is feasible with acceptable toxicity but with poor compliance in community hospitals, this trial showed that intraperitoneal CDDP compared with intravenous CDDP in combination with EPIDOX and CTX obtained a slight (not significant) improvement in progression-free survival and overall survival of optimally cytoreduced advanced ovarian cancer patients.

Adult↗
PubMed1997

Results of a European randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas.

PURPOSE: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma. METHODS AND MATERIALS: A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m2, three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization. RESULTS: Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99). CONCLUSION: Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).

Adult↗
PubMed1996

Accelerated epirubicin-ifosfamide-dacarbazine regimen in patients with adult soft tissue sarcomas.

BACKGROUND: Neutropenia and infections are the dose-limiting toxicities of the EID regimen and can cause dose reduction and/or delay in chemotherapy administration. The purpose of this study was to verify if EID + G-CSF is feasible with an acceptable toxicity in a day hospital setting and if G-CSF could allow an increase in the dose intensity of the EID regimen by shortening the intervals between the courses. PATIENTS AND METHODS: 20 patients with inoperable primary, metastatic or residual disease after surgery or at high risk of recurrence after complete resection, histologically confirmed adult soft tissue sarcoma, entered the study. The dose and schedule of the chemotherapy agents were epidoxorubicin 30 mg/m2 days 1, 2, 3, dacarbazine 300 mg/m2 days 1, 2, 3, and ifosfamide 2500 mg/m2 with mesna uroprotection days 1, 2, 3. G-CSF, 300 micrograms/day subcutaneously, was administered from day 7 for a maximum of 14 days and discontinued when WBC was greater than 10 x 10(9)/L. Courses were repeated "as soon as possible," but never earlier than 10 days from the previous course and at least 48 hours after the last G-CSF injection. RESULTS: A total of 66 EID + G-CSF courses were administered. A G3 and G4 (WHO) neutropenia occurred in 66% of evaluables courses. Nonhematological toxicity was mild. The median number of G-CSF injections required during any interval between courses was 9 (range: 4-14 injections) and the median interval between courses was 21 days (range: 13-36 days). The median dose intensity at the third course of chemotherapy was 1.15 (range: 0.71-1.62). CONCLUSION: This study shows that G-CSF allows a moderate increase in the delivered dose intensity of chemotherapy with an acceptable toxicity. Further studies are needed to investigate if this increase in DI may translate into an improved response rate.

Adolescent↗
PubMed1994

Combination chemotherapy with vinorelbine, ifosfamide, and cisplatin: a phase II study in stage IIIB-IV non-small cell lung cancer.

Forty-five stage IIIB-IV non-small cell lung cancer (NSCLC) patients entered a phase II study designed to evaluate the toxicity and the activity of a combination chemotherapy regimen consisting of vinorelbine (25 mg/m2 days 1 and 8), ifosfamide (3 g/m2 day 1 with uroprotective mesna), and cisplatin (80 mg/m2 day 1). The regimen, VIP, was administered on an outpatient basis every 3 weeks. White blood cell counts were checked weekly, and granulocyte colony-stimulating factor was administered in case of grade 4 neutropenia lasting for more than 48 hours. Leukopenia was the most frequent toxicity, with grades 3 and 4 neutropenia reported in 25% of cycles and 11 episodes of febrile neutropenia recorded in 175 evaluable courses. The combination of vinorelbine and cisplatin did not result in additive neurotoxicity: only five patients experienced grade 2 neurotoxicity after six courses of treatment. Thirty-five patients were evaluable for response. Twenty partial responses (57%) and one complete response (2.8%) were observed, for an overall response rate of 60% (95% confidence interval, 42% to 76%). The median time to progression, measured from the start of treatment, was 7 months (range, 1 to 18+), and median survival for the whole group was 12 months (range, 1 to 18+). VIP is a well-tolerated regimen and shows interesting activity in advanced NSCLC.

Adult↗
PubMed1992

Leucovorin enhances cytotoxicity of trimetrexate/fluorouracil, but not methotrexate/fluorouracil, in CCRF-CEM cells.

BACKGROUND: Increased response rates in studies of patients with colon cancer have indicated that the cytotoxic effects of fluorouracil (5-FU) are potentiated by leucovorin (LV) and by methotrexate (MTX). However, preliminary studies using a sequential combination of MTX, LV, and 5-FU showed no additional potentiation. PURPOSE: We hypothesized that the lack of additional cell kill with this combination could be due to competition of LV with MTX for cellular uptake and reduced folate polyglutamylation. We have tested this possibility by comparing the cytotoxicity of drug combinations containing MTX with that of drug combinations containing trimetrexate (TMTX), an antifolate that does not compete with LV for uptake or polyglutamylation. METHODS: Human lymphocytic leukemia CCRF-CEM cells were exposed to MTX or TMTX for 24 hours and to 5-FU during the last 4 hours of antifolate exposure. LV was administered 30 minutes before 5-FU. RESULTS: After 20 hours of exposure to TMTX or MTX, intracellular levels of phosphoribosyl pyrophosphate were elevated to a similar degree, and these levels did not decrease after a 30-minute exposure to LV. No additional cell kill was observed when LV was added to the MTX/5-FU combination, but cytotoxicity was enhanced when LV was added to the TMTX/5-FU combination. CONCLUSIONS: This study supports the hypothesis that the lack of additional cell kill when high-dose LV is added to the MTX/5-FU combination may be due to competition of MTX with LV for cellular uptake and/or competition of MTX or its polyglutamates with polyglutamylation of reduced folates. Inasmuch as TMTX does not compete with LV and reduced folates for uptake and polyglutamylation, the synergy obtained with the combination of TMTX plus 5-FU and high-dose LV further supports this hypothesis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Role of folylpolyglutamates in biochemical modulation of fluoropyrimidines by leucovorin.

The growth-inhibitory effect of fluoropyrimidines combined with a short-term exposure to leucovorin and the pattern of polyglutamylation of folates were compared between parental CCRF-CEM cells and a cell line with impaired ability to form polyglutamates (CCRF-CEM/P). The combination of leucovorin with 5-fluorouracil or 5-fluorodeoxyuridine increased the growth inhibition of CCRF-CEM cells compared to the fluoropyrimidine alone in the parent cell line but not in CCRF-CEM/P cells. In addition, leucovorin produced a significant increase in the inhibition of intracellular thymidylate synthase activity caused by 5-fluorouracil or 5-fluorodeoxyuridine as compared to these drugs alone in CCRF-CEM cells, but no increase in inhibition over that produced by the single drugs alone was observed in CCRF-CEM/P cells. Although levels of 5,10-methylene tetrahydrofolate after leucovorin administration were similar in both cell lines, polyglutamylation of this coenzyme was decreased in the CCRF-CEM/P cell line. The inability of CCRF-CEM/P cells to form significant levels of polyglutamates of N5,N10-methylenete-trahydrofolate, may be responsible for the lack of enhanced cell kill observed when a short exposure to leucovorin is used with fluoropyrimidines.

Cell Division↗
PubMed1989

Enhancement of trimetrexate cytotoxicity in vitro and in vivo by carboxypeptidase G2.

Carboxypeptidase G2 (CPG2), an enzyme produced by Pseudomonas strain RS-16, hydrolyzes the glutamate residue from methotrexate and other folates. The possibility of enhancing trimetrexate cytotoxicity by CPG2 induced folate depletion was investigated in vitro in a human leukemia cell line, CCRF-CEM, and in three sublines of these cells each with a different methotrexate resistance phenotype. The cytotoxic effect in vitro was detected using a colorimetric assay with a tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Dose-effect relationships of drugs alone and in combination were analyzed by the median effect principle and by the combination indices for quantitation of synergy or antagonism with the aid of a computer program. Trimetrexate alone was cytotoxic against the parent and all the resistant cell lines with the drug concentrations required to decrease the cell count to 50% of control in the nanomolar range (1.4, 1.6, 1.5, and 0.7 nM in CCRF-CEM, CCRF-CEM/E, CCRF-CEM/P, and CCRF-CEM/T, respectively) following 5 days of exposure. The concentration of CPG2 required to decrease the cell count to 50% control for these cell lines was 3.5, 2.6, 26.6, and 7.9 x 10(-5) units/ml for CCRF-CEM, CCRF-CEM/E, CCRF-CEM/P, and CCRF-CEM/T, respectively. A synergistic cytotoxic effect of trimetrexate after simultaneous continuous exposure with CPG2 was observed with CCRF-CEM cells and with the three resistant cell lines. This drug combination given to BALB/c x DBA/2 F1 mice bearing L1210 cells also produced synergy over a narrow range of drug doses. The activity of this combination in both methotrexate sensitive and methotrexate resistant cell lines indicates that clinical trials of this combination should be undertaken.

Animals↗
PubMed1989

Carboxypeptidase G2 enhances trimetrexate cytotoxicity in CCRF-CEM cell lines sensitive and resistant to methotrexate.

Carboxypeptidase G2 (CPG2), an enzyme produced by Pseudomonas strain RS-16, degrades folates as well as methotrexate and other folic acid analogs such as aminopterin and dichloromethotrexate, but not the "non-classical" folate antagonist trimetrexate (TMTX). The possibility of enhancing TMTX cytotoxicity of CPG2 induced depletion of intracellular folates was investigated in human leukemic CCRF-CEM cells and in three methotrexate resistant sublines of these cells with different mechanisms of resistance, CCRF-CEM/E, a subline with increased DHFR; CCRF-CEM/P, a subline defective in polyglutamylation and CCRF-CEM/T, a subline with impaired MTX uptake. The cytotoxic effect was detected using a colorimetric assay with MTT. Dose-effect relationships of single drugs alone and in combination were analyzed by the median effect principle and by the combination indices for the quantitation of synergism or antagonism with the aid of a microcomputer. TMTX alone was very effective on the parent and all the resistant cell lines (CCRF-CEM/E, CCRF-CEM/P, CCRF-CEM/T) with ED50 values in the nanomolar range (1.4, 1.6, 1.5 and 0.7 nM, respectively) following 5 days of exposure. The ED50s of CPG2 for these cell lines were 3.5, 2.6, 26.6 and 7.9 X 10(-5) U/ml, respectively. A synergistic cytotoxic effect of TMTX after simultaneous continuous exposure was observed with CPG2 on CCRF-CEM cells and on the three resistant cell lines.

Antineoplastic Agents↗
PubMed1989

Sequence-dependent enhancement of HCT-8 cell kill by trimetrexate and fluoropyrimidines: implications for the mechanism of this interaction.

The new folate antagonist trimetrexate is an inhibitor of dihydrofolate reductase, but unlike methotrexate (MTX) it is not polyglutamylated. We have compared the cell killing effects of MTX and trimetrexate/5-fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) combinations on HCT-8 cells in vitro, in an attempt to explore indirectly the role of polyglutamylation of the antifol in determining the known sequence-dependent synergism between MTX and FUra. The comparisons were made in a number of equitoxic concentrations and times of exposure. Trimetrexate given for 4, 24 or 48 h followed by FUra, for 4, 24 or 196 h, produced synergistic HTC-8 cell kill, whereas antagonism was observed when FUra preceded or was given simultaneously with trimetrexate. The degree of interaction was essentially identical to those obtained when MTX was combined with FUra. The interactions between MTX/FdUrd and trimetrexate/FdUrd were also similar: synergistic cell kill resulted from the sequences trimetrexate or MTX followed by FdUrd, while additive effects were produced by trimetrexate or MTX + FdUrd combinations or FdUrd followed by MTX or trimetrexate. Because the same interactions observed with MTX/FUra or FdUrd combinations were also obtained when trimetrexate was combined with the fluoropyrimidines, it is unlikely that polyglutamylation of the antifols plays a significant role in determining the different sequence-dependent effects of these antimetabolites. However, these studies do not rule out the possibility that increased levels of dihydrofolate polyglutamates increase fluoropyrimidine cytotoxicity.

Adenocarcinoma↗
PubMed1986

Regional chemotherapy by a totally infusion pump preceding radiotherapy in advanced cervical carcinoma: a preliminary report.

The authors report the preliminary results of a prospective study on intra-arterial chemotherapy and radiotherapy of advanced cervix carcinoma. The drugs were delivered by a totally implanted Infusaid Model 400 pump and patients received cyclic therapy consisting of Cis-Platinum, Methotrexate and Bleomycin. The catheter tips were positioned during a laparotomy in the hypogastric arteries with sutures and the pump was implanted in a subcutaneous pouch in the abdomen. After chemotherapy all patients had radiotherapy. Five patients entered in the study. Preliminary results suggest that long-term intra-arterial infusion chemotherapy for the treatment of advanced cervix carcinoma is practical for many patients. Two of five patients, after intra-arterial chemotherapy and radiotherapy, had radical hysterectomy.

Adult↗
PubMed1985

[Recent pharmacotoxicologic and clinical findings on adriamycin].

Anthracycline derivative adriamycin (ADR) is one of the most important anticancer drugs with major clinical application in carcinomas of the brest, endometrium, ovary, testicle, thyroid, lung and in treatment of many sarcomas. It is useful also in haematological cancers including acute leukaemia, multiple myeloma, Hodgkin's disease and the diffuse non-Hodgkin lymphomas. A factor limiting ADR clinical practice is represented by a severe dose-dependent cardiac toxicity, the mechanism of which is still under study, but appears to involve excessive intracellular production of free radicals within myocardium: this is rarely seen at ADR dosage below 500 mg/m2. A series of new anthracycline analogues has recently entered clinical trials: they include 4'-epiadriamycin, 4'-deoxy-adriamycin, aclacynomycin A, carminomycin and N-trifluoroacetyladriamycin-14-valerate. These new agents appear to have different spectrum of action and somewhat less toxicity, however antitumor activity in only now being defined, consequently major clinical interest is still concentrated in the use of ADR. The present article reviews the most relevant data from literature concerning the pharmacology, the toxicology and the clinical use of ADR.

Alcohol Oxidoreductases↗