Evidence of activity of Irinotecan in patients with advanced AIDS-related Kaposi's sarcoma.

Fourteen HIV-infected patients with advanced Kaposi's sarcoma (KS) received Irinotecan 150 mg/m intravenously on days 1 and 10. All patients were relapsed/progressed during highly active antiretroviral therapy, administered as primary antineoplastic therapy. An objective response, all partial remissions, occurred in 75% of patients. Irinotecan was well tolerated, severe leukopenia occurred in only 33% of patients. In HIV-infected patients with advanced KS, irinotecan is active and well tolerated.

Neoadjuvant accelerated chemotherapy followed by hyperfractionated radiation therapy in patients with operable, locally advanced head and neck carcinoma.

A prospective phase II trial was carried out to evaluate an accelerated chemotherapy (CT) regimen followed by hyperfractionated radiation therapy (RT) in previously untreated Stage III-IV, operable (total laryngectomy), head and neck cancer patients. The current study evaluates overall survival, loco-regional control, organ preservation rates and toxicity. Between April 1997 and December 2002, 68 patients with advanced head and neck cancer were treated with 3 cycles of induction CT (cisplatin and 5-fluorouracil; days 1, 14, and 28) followed by hyperfractionated RT (7440 cGy/62 fractions). Sixty patients received the planned RT-CT treatment. Two months after the end of RT, 96% of patients had a clinical complete remission of the primary and 66% of the neck disease. At a median follow-up of 32 months, the 3-year overall and disease-free survival rates were 66% and 76%, respectively. Seven patients recurred on the primary site, 1 on the neck and 2 patients only had distant metastases. The organ preservation rate was 73%. Acute grade 3-4 mucositis occurred in 75% of patients and an 18% rate of CT-related cardiotoxicity was reported. The accelerated CT-RT regimen achieves a high rate of larynx preservation albeit with considerable toxicity. The current prospective clinical trial was approved by the Ethics Committee of the Centro di Riferimento Oncologico (C.R.O.) on May 27, 1996, # CRO-02-96. Written informed consent was required from all patients entering the study.

Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study.

BACKGROUND/AIMS: The aim of this study is to verify the efficacy and safety of peg-interferon alfa-2b in combination with ribavirin for initial treatment of HCV-associated mixed cryoglobulinemia. METHODS: Eighteen patients (7 women and 11 men) affected by mixed cryoglobulinemia were included in the study and treated with peg-interferon alfa-2b 1.0 microg/kg once a week plus ribavirin (1000 mg daily) for 48 weeks, regardless of the HCV genotype. RESULTS: At the end of the treatment HCV-RNA became undetectable in 15 patients (83%) and most patients improved clinically. One subject suspended treatment at 13th week due to depression. A large fraction of the patients (8 cases: 44%) relapsed both virologically and clinically a few weeks after the end of therapy. At the end of follow-up, only eight patients (44%) obtained a sustained virological response. CONCLUSIONS: Peg-interferon alfa-2b in combination with ribavirin seems safe and useful for patients affected by mixed cryoglobulinemia, but not as effective as in patients with HCV-positive chronic hepatitis without cryoglobulinemia.

Pharmacokinetic interaction between chemotherapy for non-Hodgkin's lymphoma and protease inhibitors in HIV-1-infected patients.

OBJECTIVES: We have investigated whether chemotherapy for HIV-related systemic non-Hodgkin's lymphoma (NHL) affects the pharmacokinetics of protease inhibitors. PATIENTS AND METHODS: This was a prospective, open-label, non-randomized, two-way crossover trial in HIV-1-infected patients treated with highly active antiretroviral therapy and chemotherapy for NHL. Seven patients received indinavir at a dosage of 800 mg three times daily and three patients received nelfinavir at a dosage of 750 mg three times daily. Chemotherapy consisted of adriamycin, cyclophosphamide, vincristine and prednisolone (CHOP). Each patient had blood samples for protease inhibitor pharmacokinetics drawn concomitantly with or independently of the CHOP cycle. RESULTS: When indinavir was given concomitantly with CHOP, the AUC(0-8) increased by 38% (20.5 +/- 9.0 versus 14.9 +/- 9.5 mg.h/L; P=0.03), and was comparable to historical controls. By contrast, the AUC(0-8) of indinavir administered without CHOP was lower than expected. A similar trend was observed with nelfinavir. Likewise, we observed a significant number of patients with C(0) and C(8) below the IC(50) for the wild-type virus (0.1 mg/L) when the drug was administered without CHOP. CONCLUSIONS: Therapeutic drug monitoring of protease inhibitors should be part of the work-up in HIV-infected patients receiving chemotherapy for NHL.

Evaluation of three molecular biology-based assays for the detection of GB virus C/hepatitis G virus in clinical specimens.

OBJECTIVE: The present study was performed to evaluate the reliability of three reverse transcription-polymerase chain reaction (RT-PCR) assays, one commercial and two 'homebrew', for GB virus C (GBV-C)/hepatitis G virus (HGV) RNA detection in clinical specimens. We, therefore, investigated the virus prevalence with the method that gave us the best performances. METHODS: The commercial assay amplified sequences from the viral 5'-untranslated region (5'UTR) and non-structural 3 (NS3) region. The non-commercial assays 1 and 2 were based on different primers for the 5'UTR consensus sequence. RESULTS: The percentage of overall concordance by the three methods was 91.7%, raising to 93.0% when only the two non-commercial methods were compared. Assay 1 showed low sensitivity (57.1% vs. the commercial assay, 58.8% vs. assay 2), with 100% specificity. The commercial assay gave 18 of 54 (33.3%) 'false-negative' results, concordantly negative by the other assays. The prevalence of GBV-C/HGV RNA among the HIV+ patients was 27.0 and 32.6% in HIV/HCV co-infected patients. CONCLUSION: These data suggest that assay 2 has higher reliability as compared to the other two methods and may be used for an accurate GBV-C/HGV RNA detection in clinical and epidemiological studies.

Improvement of systemic human immunodeficiency virus-related non-Hodgkin lymphoma outcome in the era of highly active antiretroviral therapy.

To assess the impact of highly active antiretroviral therapy (HAART) on the outcome of systemic human immunodeficiency virus-related non-Hodgkin lymphoma (HIV-NHL), we retrospectively analyzed 235 patients in whom HIV-NHL was diagnosed from April 1988 through December 1999. A multivariate Cox proportional hazards model was used to estimate prognostic factors for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Complete remission occurred in 49% of patients, and the 3-year rates of OS, PFS, and DFS were 19%, 49%, and 73%, respectively. The greatest risk for shortened OS, PFS, and DFS was associated with no HAART use (compared with long-term HAART use); hazard ratios were 17.42 (95% confidence interval [CI], 17.42-40.25), 9.11 (95% CI, 3.71-22.32), and 8.54 (95% CI, 1.19-61.11), respectively. Our study suggests that the long-term use of HAART may favorably change the outcome for patients with systemic HIV-NHL.

Impact of concomitant antiblastic chemotherapy and highly active antiretroviral therapy on human immunodeficiency virus (HIV) viremia and genotyping in HIV-infected patients with non-Hodgkin lymphoma.

We evaluated the replication and resistance patterns of human immunodeficiency virus (HIV) strains recovered from HIV-infected patients with non-Hodgkin lymphoma (NHL) who were receiving chemotherapy (CT) concomitant with highly active antiretroviral therapy (HAART). We analyzed virological response to HAART in 35 patients with HIV and NHL who were treated with a cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy regimen and HAART and the virological response in 26 HIV-infected patients with CD20 cell-positive NHL who were treated with rituximab and cyclophosphamide-doxorubin-etoposide therapy. Genotype and virtual phenotype analyses were performed at baseline and when virological failure occurred. Only 9 patients met the criteria for virological failure. Genotype and virtual phenotype analyses demonstrated that, during CT administration, new mutations might occur, but there were no significant changes in the preexisting resistance patterns. Our data show that combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of patients receiving this treatment.

Quantification of hepatitis C virus (HCV) in liver specimens and sera from patients with human immunodeficiency virus coinfection by using the Versant HCV RNA 3.0 (branched DNA-based) DNA assay.

The new generation assay Versant HCV RNA 3.0v (Bayer Diagnostics) was evaluated to quantify hepatitis C virus (HCV) RNA levels in liver biopsy specimens from patients with HCV and human immunodeficiency virus (HIV) coinfection. A total of 25 liver biopsies and sera collected at the time of liver biopsy were used. The efficiency of HCV RNA recovery from spiked samples was between 38.6 and 50.7%, and reproducible measurements of viral load were observed (the intra- and interrun coefficients of variation were 0.5 to 13% and 3.5 to 24.7%, respectively), with good specificity and sensitivity. Linearity was evaluated in the range of 96,154 to 769 IU/ micro g by using a serially diluted high-titer sample. Coinfected patients had high HCV RNA viral loads in serum and liver (498,471 IU/ml and 231,495 IU/ micro g, respectively), and both levels were correlated (r = 0.63; P < 0.01). The amount of hepatic HCV RNA was significantly higher among patients with genotype 1 than among patients with genotype 3 (P < 0.01). The virological end-of-treatment response in the serum was associated with a lower pretreatment intrahepatic HCV viral load (P = 0.03). The new version of b-DNA is a sensitive, specific, and reproducible method for quantitating HCV RNA in the liver. Given its positive analytical performance, the assay will be used to evaluate the HCV RNA levels in the serum and liver during follow-up of patients treated with an anti-HCV therapeutic regimen.

Virological efficacy in HIV-infected patients affected by non-Hodgkin lymphoma, treated with antiblastic chemotherapy and highly active antiretroviral therapy.

This study evaluated replication of human immunodeficiency virus (HIV) and the genotypic resistance pattern in 26 HIV-infected patients affected by non-Hodgkin lymphoma who were treated with at least 3 cycles of chemotherapy (CT; rituximab and CDE) and highly active antiretroviral therapy (HAART). Genotyping was performed at baseline and when virological failure occurred. Six patients met the virological failure criteria. The genotyping analysis demonstrated that during CT administration new mutations might occur, but no significant changes in the pre-existing resistance patterns were observed. The data show that a combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of such patients.

Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection.

A phase 2 prospective study was performed to evaluate the feasibility and activity of a short, dose-intensive chemotherapy regimen and radiotherapy (the Stanford V regimen) plus highly active antiretroviral therapy (HAART) and granulocyte colony-stimulating factor (G-CSF) support in patients with Hodgkin disease and HIV infection. Fifty-nine patients were enrolled. Stanford V was well tolerated and 69% of the patients completed treatment with no dose reduction or delayed chemotherapy administration. The most important dose-limiting side effects were bone marrow toxicity and neurotoxicity. Complete remission was achieved by 81% of the patients, and after a median follow-up of 17 months 33 patients (56%) were alive and disease-free. The estimated 3-year overall survival (OS), disease-free survival (DFS), and freedom from progression (FFP) were 51%, 68%, and 60%, respectively. Probability of FFP was significantly (P =.02) higher among patients with an International Prognostic Score (IPS) of 2 or lower than in those with an IPS higher than 2, and the percentages of FFP at 2 years in these groups were 83% and 41%, respectively. Similarly, the probability of OS was significantly (P =.0004) different in the 2 groups, and the percentages of OS at 3 years were 76% and 33%, respectively. Our data confirm that the Stanford V regimen with concomitant HAART is feasible and active in an HIV setting. However, a more intensive approach should be considered in patients with high IPSs.