PubMed Health⌕ Search

Biomedical subjects

M Airoldi

Publications and source records attributed to M Airoldi.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacokinetic evaluation of gemcitabine and 2',2'-difluorodeoxycytidine-5'-triphosphate after prolonged infusion in patients affected by different solid tumors.

BACKGROUND: The study determined pharmacokinetic parameters, toxicity profile and preliminary clinical activity of gemcitabine administered i.v. at different infusion rates in patients with a range of solid tumors. PATIENTS AND METHODS: Twenty patients were enrolled for both pharmacokinetic and clinical studies. Gemcitabine 300 mg/m(2) was administered during 1 h, 2 h or 3 h, and as a conventional dose of 1000 mg/m(2) during 30 min infusion. Administration was on days 1, 8 and 15 every 4 weeks. RESULTS: Patients were randomly assigned to one of the four arms. After 30 min infusion of 1000 mg/m(2) gemcitabine the plasma concentration remained above the saturation level of 10-20 microM, whereas after 1, 2 or 3 h infusion 300 mg/m(2) gemcitabine it remained below the saturation level for most of the time (being in the range 2.5-10 microM). Gemcitabine triphosphate was determined in the four arms in white blood cells; for infusion times from 0.5 to 3 h there was a progressive enhancement of gemcitabine triphosphate levels. In all evaluable patients the toxicity was mild, myelosuppression being the main toxicity. No grade 3 or 4 toxicities occurred. Clinical response was similar in patients receiving 300 mg/m(2) gemcitabine in 2 and 3 h and in the 1000 mg/m(2) arm. CONCLUSIONS: 300 mg/m(2) gemcitabine during 3 h infusion produced the highest accumulation of gemcitabine triphosphate. Thus, to achieve the highest possible gemcitabine triphosphate level, prolonged infusion time would appear to be more important than a high dose administered as a short infusion. However, there was no substantial difference in toxicity or antitumoral activity in the all different patient groups.

Adult↗
PubMed2005

Current role of chemotherapy in exclusive and integrated treatment of malignant tumours of salivary glands.

In the management of salivary glands carcinomas, surgery is the treatment of choice. Post-operative radiotherapy is indicated in cases with high risk of loco-regional relapse. Radiotherapy is also standard treatment in cases that are inoperable at onset. Chemotherapy plays a palliative role. Today, the integration between radiotherapy and chemotherapy, which provides increased local control, represents a significant step forward. This integration is important since 5-year survival in tumours with high grade histology is approximately 50%. Overall incidence of metastases is approximately 25%. Primary locations of metastases are lungs, liver, bone, central nervous system and other organs. In cases of metastatic disease, chemotherapy plays only a palliative role.

Combined Modality Therapy↗
PubMed2003

Ifosfamide in the treatment of head and neck cancer.

Ifosfamide (IFO) has demonstrated activity in recurrent/metastatic squamous cell head and neck carcinoma with an overall response rate of 24-26%. Better results are reported for chemotherapy-naive patients; in heavily pretreated cases results are poor and toxicity unacceptable. Cisplatin-IFO combination in stage III-IV is probably more active than IFO alone (ORR = 60-72 vs. 50%) but is indicated in patients who desire aggressive treatment and are physically able to tolerate the drugs. The carboplatin-IFO scheme is better tolerated than the cisplatin-IFO regimen with superimposable clinical results (ORR = 69%; CR = 15%). Carboplatin-taxol-IFO is one of the most active regimens in recurrent (ORR = 59%; CR = 17%) and in locally advanced (ORR = 81%; CR = 31%) head and neck cancer. Its role in the multidisciplinary treatment of advanced head and neck cancer is under investigation. In recurrent/metastatic undifferentiated nasopharygeal carcinoma, IFO combinations have proven to be effective as first- and second-line treatment.

Antineoplastic Agents, Alkylating↗
PubMed2003

Update and perspectives on non-surgical treatment of salivary gland malignancies.

Surgery is the treatment of choice for major and minor salivary gland malignancies. Herein, the role of radiation and medical treatment in the multidisciplinary management of salivary gland tumours is discussed. Neutron irradiation and hyperfractionated external beam mega voltage irradiation improve local control. Combination of three dimensional conformal radiotherapy and intensive-modulated radiation therapy provide better local tumour delineation, better field design to encompass the tumour allowing dose escalation to target while sparing the surrounding normal tissue. Cisplatin-based chemotherapy provides a response rate > or = 45%, in a palliative setting. Concomitant chemo-radiotherapy could improve local control. Recent studies evaluated the expression of molecular targets in salivary gland carcinomas (c-kit = 53-90%, EGFR = 25-85%, c-erb-B2 = 11-58%, p53 = 11-67%, H ras = 18%); these targets are very important since new targeted drugs are now available. Anti-androgen therapy might have a role in the management of patients with ductal carcinoma. These new targeted drugs could be integrated with chemotherapy and radiotherapy in the treatment of locally advanced/metastatic salivary gland malignancies.

Adult↗
PubMed2003

Oropharyngeal carcinoma during pregnancy: clinical and psycho-oncological aspects.

Cancer is uncommon in pregnancy, occurring in approximately one out of 1000 pregnancies, although it has been noted that one out of 118 women diagnosed with cancer is pregnant at the time of diagnosis. In the last 10 years, two oropharyngeal carcinomas, (1 squamous cell carcinoma and 1 adenoid cystic carcinoma) which developed during pregnancy, have been diagnosed and treated in our Department. No cases of oropharyngeal cancer, during pregnancy, have so far been reported in the literature with the exception of one case of oral cancer. This report focuses not only on the clinical history but also the management of oropharyngeal carcinoma during pregnancy, in terms of choice and timing of treatment. A scrupulous psycho-oncological analysis was also carried out in order to throw further light on psychological repercussions of head and neck cancer in the pregnant woman.

Adult↗
PubMed2001

Phase II randomized trial comparing vinorelbine versus vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies.

BACKGROUND: Some previous studies have shown that vinorelbine (VNB) is active in recurrent salivary gland tumors. METHODS: Between April 1993 and April 1997, 36 patients in a Phase II randomized trial received either cisplatin, 80 mg/m(2), on Day 1 plus VNB, 25 mg/m(2), on Days 1 and 8 (every 3 weeks) (for a minimum of 3 cycles (Arm A [16 patients]), or VNB, 30 mg/m(2)/week, (for a minimum of 9 wks) (Arm B [20 patients]). There were 23 males and 13 females with a median age of 59 years (range, 20-74 years) and a median Eastern Cooperative Oncology Group performance status of 1 (range, 0-2). Four patients had been treated with prior surgery (S) or radiotherapy (RT), 27 patients had been treated with S plus RT, and 5 patients had been treated with S plus RT plus mitoxantrone. Eighteen patients had major salivary gland tumors, and 18 patients had minor salivary gland tumors; 9 patients had adenocarcinoma, 22 patients had adenoid cystic carcinoma, 1 patient had a malignant mixed carcinoma, 3 patients had undifferentiated carcinoma, and 1 patient had a mucoepidermoid carcinoma. The site of recurrence was local in 16 patients, local plus metastatic in 5 patients, and metastatic only in 15 patients. These characteristics were well balanced between the 2 arms. RESULTS: In Arms A and B a complete response (CR) was noted in 3 patients (19%) and no patients, respectively; a partial response (PR) was noted in 4 patients (25%) and 4 patients (20%), respectively; no change was noted in 6 patients (37.5%) and 9 patients (45%), respectively; and progressive disease was noted in 3 patients (19%) and 7 patients (35%), respectively. The median duration of the CR was 15+ months (range, 6-27+ months) and for PR the median duration was 7.5 months (range, 3-11+ months) and 6 months (range, 3-9 months) in Arms A and B, respectively. Number of patients surviving > 12 months was 6 versus 1 in Arms A and B, respectively (P < 0.05). Grade 2-3 nausea and emesis was statistically higher (P < 0.001) in Arm A; there was no significant difference with regard to other side-effects between the two treatment arms. CONCLUSIONS: VNB is a drug with moderate activity in salivary gland malignancies. The combination of cisplatin plus VNB was found to be more active than VNB alone, with a good number of CRs and long-term survivors reported in the current study.

Adult↗
PubMed2001

Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy.

The emergence of mutations encoding drug resistance is supposed to be a significant limitation to the clinical efficacy of inhibitor compounds directed against specific HIV-1 enzymatic targets. We have used a commercial test (Visible Genetics Inc., Paris, France) to study the prevalence of mutations occurred in HIV-1 protease and reverse transcriptase (RT) genes in 93 HIV-1 infected patients treated with at least one regimen containing a protease inhibitor (PI) and failing to the current therapeutic regimen. Protease mutations conferring resistance to at least one PI were detected in 46/93 (49.4%) of strains, 25 (26.8%) of which showed resistance to all PIs. Reverse transcriptase mutations conferring resistance to at least one RT inhibitor were detected in 57/93 (61.2%) of strains, 18 (19.3%) of which showed resistance to all RT inhibitors. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). Twelve of our patients (12.9%) had no mutation encoding drug resistance and were completely sensitive to all RT and protease inhibitors. Therefore, not all virological failures are caused by HIV-1 genomic resistance.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Survival in patients with recurrent squamous cell head and neck carcinoma treated with bio-chemotherapy.

BACKGROUND: We have shown that rIL-2 administration in recurrent head and neck cancers induces a tumor-specific T-lymphocyte reactivity and tumor regression; in a pilot study we have shown a safe and effective administration of rIL2 after cisplatin + 5-fluorouracil. Long-term results are not known. METHODS: Thirty patients with recurrent-persistent head and neck cancer were treated with cisplatin (100 mg-m(2)) d.1,5-fluorouracil (1 gr-m(2)-d c.i. 96 h), and SQ rIL-2 (4.5 M IU day 8 to 12 and 15 to 19) every 3 weeks. RESULTS: The overall response rate was 53.3% (95% CI; 34.4-72.3%): 26.6% complete response (CR) (8 patients) and 26.6% partial response (PR) (8 patients); 6 patients had SD (20%), 8 had PD (26.6%). The median follow-up was 36 months (range, 28-44). The median CR duration is 16.2 months (8.5-39+); the median survival duration of this group has not been reached. The median PR duration was 7.2 months (3-10); the median survival was 13.3 months (10-26). The median overall survival was 14 months. CONCLUSIONS: The most impressive finding is the very long survival of CRs patients. This outcome has been reported in other cancer patients with a CR after IL-2 therapy.

Adult↗
PubMed2001

Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma.

BACKGROUND: Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. METHODS: Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 x 10(6)/kg (range, 4.5-18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m(2)/d, + carboplatin, 300 mg/m(2)/d, + VP-16, 300 mg/m(2)/d days 1 through 4. RESULTS: After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%),1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14-50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. CONCLUSIONS: HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs.

Adult↗
PubMed2001

Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside resistance in an Italian group of antiretroviral multiexperienced patients.

Multiple nucleoside resistance involves specific genetic changes in the HIV-1 reverse transcriptase gene, such as Q151M mutation and an insertion of two serine aminoacids at RT codon 69. Among 432 patients failing antiretroviral therapy, five (1.15%) harboured viruses with Q151M mutation into the RT gene and no viruses were identified harbouring insertion at codon 69. Also we have studied the long-term benefit of HIV genotypic testing with the failure to reach a viral load below 50 copies/ml within 1 year of antiretroviral therapy using as the primary end-point. A group of 64 HIV-positive antiretroviral multiexperienced patients were examined, all of them failing the current ART. HIV-RNA changed -0.8 log at month 4 and +0.1 log and -0.5 log at months 8 and 12, respectively. The proportion of patients with viral load below 50 copies/ml was 19.3, 32.8, and 28.1% at months 4, 8, and 12, respectively. In multidrug-experienced patients, genotype-guided therapy is not in fact able to achieve complete viral suppression in more than 30% of patients after 1 year of ART. The development of more precise resistance tests and interpretations are needed for better control of HIV replication. Other metabolic/pharmacokinetics factors of poor drug adherence should also be assessed.

Acquired Immunodeficiency Syndrome↗
PubMed2001

A preliminary pharmacokinetic study of docetaxel, carboplatin and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck.

This work investigates the pharmacokinetics and toxicity resulting from the concomitant use of low dose carboplatin (CBCA)/docetaxel (DTX) plus concurrent radiotherapy in patients with head and neck cancer. The study comprised 11 patients with stage III-IV head and neck cancer. All patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 70 Gy over 7 weeks. CBCA (AUC 0.4 mg/ml, min/day) was also administrated as 20 min i.v. infusion, starting 1 day before the first radiotherapy fraction. CBCA was administered for 5 consecutive days every 2 weeks (weeks 1, 3, 5 and 7). DTX 30 mg/m2 (1 h i.v. infusion) was given as a single dose on days 10, 24 and 38. CBCA on day 1 and DTX on day 10 were analysed to determine the concentration-time curves during the first 24 h. CBCA Cmax and Cmin in 2-5 days and on day 15 and 29, as well as total plasma platinum on days 2, 3, 4, 5, 29 and 43 were also assayed. By calculating the non-compartmental pharmacokinetic parameters of the two drugs from the available plasma concentrations we found in the first week values similar to those reported in the literature as single agents. In contrast, during subsequent weeks (weeks 3 and 5), a significant and progressive increase of platinum levels was observed. So, it could be assumed that after 2 weeks of CBCA and DTX treatment a bias in dose calculation occurred because the linear relationship between creatinine clearance (used to calculate the expected AUC through the Calvert formula) and CBCA clearance was no longer observed.

Antineoplastic Agents↗
PubMed2001

A sequence-dependent combination of docetaxel and vinorelbine: pharmacokinetic interactions.

We studied possible pharmacokinetic interactions between docetaxel (DTX) and vinorelbine (VNR) in patients affected by different types of cancer. Patients with metastatic breast cancer or recurrent head and neck cancer received the following schedules: Protocol A: 11 patients were i.v. infused for 1 h with DTX (80 mg/m2) at once, followed by VNR (25 mg/m2) as slow i.v. bolus; Protocol B: VNR (25 mg/m2) as a slow 10 min i.v. bolus was administered to 12 patients, immediately followed by 1 h i.v. infusion of DTX (80 mg/m2). In both schedules, VNR and DTX plasma concentrations versus time were analysed by HPLC obtaining the corresponding non-compartmental pharmacokinetic parameters. VNR appeared pharmacokinetically affected by the sequential administration of DTX, since with protocol B, Cmax and AUC were significantly higher and clearance lower than in protocol A. Moreover, a significant increase in the VNR plasma level was observed in correspondence with the peak plasma level of DTX. By contrast, Cmax, AUC and clearance of DTX did not vary in the two protocols. Also the number of neutrophils at nadir on day 8 of treatment varied significantly in the two schedules. In conclusion we observed altered pharmacokinetic parameters between protocol A (DTX, VNR) and protocol B (VNR/DTX). In particular, patients following protocol B seemed to be exposed to higher VNR plasma concentration and to higher haematological toxicity.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Clinical and pharmacokinetic data of a docetaxel-epirubicin combination in metastatic breast cancer.

In order to explore activity and pharmacokinetic data of a docetaxel-epirubicin combination we analyzed a population of 60 metastatic breast cancer patients. All the patients had an ECOG performance status < 3; 41 patients (68%) had visceral metastases as dominant site of disease, including 33% with liver metastases. Three or more involved organs were present in 43% of patients; 35% had received prior hormonotherapy; 10% for metastatic disease. Twenty-five patients (42%) had received prior adjuvant chemotherapy; 15% a CAF regimen. Twenty per cent of patients had less than 12 months disease-free interval. Docetaxel and epirubicin were both given at a dose of 75 mg/m2 i.v. d. 1 every 3 weeks. After a median of six cycles we had 5 CR (8.3%), 40 PR (66.6%), 7 NC (11.6%), and 8 PD (13.3%). Response rates in patients with visceral and liver metastases were 78% and 55% respectively. Premenopausal status, < 1 year disease free survival and > 3 metastatic sites were associated with a lower response rate. After a median follow-up of 19 months (12-36), median disease-free survival is 11 months and median overall survival has not been reached. Grade 4 neutropenia was observed in 75% of courses but with febrile neutropenia in 6.2% of courses only. Non-hematologic toxicity wasn't clinically important. A NYHA class III reversible cardiac failure was observed in one patient (1.6%). The pharmacokinetic evaluation in 16 patients has shown that docetaxel transiently interfered with epirubicin plasma level when docetaxel was administered 1 h after epirubicin.

Adult↗
PubMed2001

HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment.

The prevalence and clinical implications of the Q151M multidrug-resistance mutation gene (mut) to antiretroviral drugs in the HIV reverse transcriptase (RT) gene have not yet been fully explained. In the present study three out of 350 (0.85%) of HIV-infected patients who underwent a drug-resistance genotyping assay because of therapeutic failure showed the Q151M mut. All these patients had been previously treated with zidovudine in association with didanosine. One such patient failed to respond to all salvage regimens tried and was shown to harbour some of the characteristic mut associated with Q151M (77L and 116Y). Another two patients partially responded to salvage regimens, both virologically and immunologically, and harboured the M184V mut in the RT gene. The prevalence of Q151M mut in our group was less (0.85%) than in other studies, which ranged from 2 to 19%. The M184V mut seemed to confer some viro-immunological benefit when associated with the Q151M mutation, compared with the latter alone.

Adult↗
PubMed1999

Carcinoma of the larynx in the elderly: analysis of potentially significant prognostic variables.

The incidence reported for carcinomas of the head and neck currently peaks between the sixth and seventh decades of life. In this retrospective study we were interested in learning whether age is a potentially significant prognostic factor for survival. We considered a set of variables in a series of 134 patients, divided into two groups; between 65 and 70 years of age, and older than 70. Stage I-II tumors were present in 44 patients, while locally advanced lesions (stages III-IV) were present in 90. Statistical analysis of survival was performed using the actuarial survival rates according to Kaplan-Meier; significance was evaluated using the log-rank test. Multivariate analysis was performed according to the Cox logistic regression model to determine the prognostic significance of any of the variables. Univariate analysis was performed on a series of variables regarding the patient, tumor and treatment. In the younger group, age appeared to be a favorable prognostic factor. Tumor size had a significant effect on disease-free survival, both globally and between the two groups (p < 0.05). Lymph node status substantially influenced the five-year survival rate (p = 0.001). Tumor invasion of the lymph nodes led to a difference between the two groups. Survival was lower in the younger than in the older group. There was a significant difference (p < 0.01) in survival between patients who had undergone surgery (75%) and those who received radiotherapy alone (33%). Multivariate analysis of these variables showed that disease stage, and treatment of lymph nodes were both significant (p = 0.0016 and p = 0.0002, respectively). Survival rates for the so-called "young elderly" (65-70 years) are generally higher than that for those aged 70 and over. Following accurate and comprehensive assessment by the anesthesiologist and the internist, and appropriate adjustment of the patient's nutritional and metabolic status, combined radical surgery and radiotherapy can and must be performed. Minimal palliative interventions, in the belief that tumor growth is biologically less aggressive in the elderly patient, should be avoided.

Aged↗
PubMed1999

Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethyl-L-arginine in mice intranasally infected.

To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production, on regulation of inflammatory responses to Bordetella pertussis infection, mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decrease of cellular accumulation of neutrophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally. In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitoneally) for 5 consecutive days showed higher mortality rate than untreated mice infected with B. pertussis, and the number of B. pertussis in lungs of mice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B. pertussis.

Animals↗