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Increasing amounts of intracellular adhesion molecule 1 (ICAM 1) in the blood of HIV-infected patients with Kaposi's sarcoma (KS) may be a sign of declining immune function. ICAM 1 is a molecule on the surface of white blood cells that allows them to attach to other cells. Levels of ICAM 1 were measured in blood samples drawn from 64 HIV-infected individuals, 27 of whom had KS. ICAM 1 levels were significantly higher in the KS patients compared to the other HIV-infected individuals. During the two- to four-year follow-up, CD4 counts dropped more than 50% in 16 of the KS patients. Retrospective analysis revealed that these patients had significantly higher ICAM 1 levels at the beginning of the study than KS patients whose CD4 counts declined less than 50%. KS lesions may cause ICAM 1 to be shed into the blood, or the infectious agent allegedly responsible for the disease may cause ICAM 1 shedding.

Cancer is the second leading cause of death during the reproductive years complicating between 0.02% and 0.1% of pregnancies. The incidence is expected to rise with the increase in age of childbearing. The most common types of pregnancy-associated cancers are: cervical cancer, breast cancer, malignant melanoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma and ovarian cancer. The relatively rare occurrence of pregnancy-associated cancer precludes conducting large, prospective studies to examine diagnostic, management and outcome issues. The treatment of pregnancy-associated cancer is complex since it may be associated with adverse fatal effects. In pregnant patients diagnosed with cancer during the first trimester, treatment with multidrug anti-cancer chemotherapy is associated with an increased risk of congenital malformations, spontaneous abortions or fetal death, and therefore, should follow a strong recommendation for pregnancy termination. Second and third trimester exposure is not associated with teratogenic effect but increases the risk of intrauterine growth retardation and low birth weight. There are no sufficient data regarding the teratogenicity of most cytotoxic drugs. Almost all chemotherapeutic agents were found to be teratogenic in animals and for some drugs only experimental data exist. Moreover, no pharmacokinetic studies have been conducted in pregnant women receiving chemotherapy in order to understand whether pregnant women should be treated with different doses of chemotherapy. This article reviews the available data regarding the different aspects of the treatment of cancer during pregnancy.

Antiblastic treatment of hematological malignancies during pregnancy poses a number of issues related to the curability of the maternal disease, the need of a prompt treatment and the potential toxicity of chemotherapy for the fetus. Here we report the results of a systematic literature search about the management of the most frequent hematological malignancies that may occur during pregnancy, focusing on specific issues related to gestational age at diagnosis, fetal toxicity and efficacy on the maternal side. The standard approach in non-pregnant women is illustrated as reference.

At least one in a thousand pregnancies is complicated by cancer and, as the maternal age at pregnancy increases, numbers are growing. If chemotherapy cannot be postponed, both doctors and patients face complex medical and ethical issues. There is a conflict between optimal maternal therapy and fetal wellbeing. Treatment during the first trimester increases the risk of congenital malformations, spontaneous abortions and fetal death. Second and third trimester exposure is less risky, but it can cause intrauterine growth retardation and low birth weight. Other effects on pregnancy after the first trimester include premature birth, stillbirth, impaired functional development, myocardial toxicity and myelosuppression. Counseling and management of these cases are difficult, because literature is mostly represented by case reports or retrospective series while randomized prospective studies or guidelines are lacking. Moreover, personal experience is often scanty due to the rarity of the condition. This article reviews the available data regarding the different aspects of systemic treatment of cancer during pregnancy to help oncologist and obstetricians in counseling their patients and treat them accordingly.

Background Bronchioloalveolar carcinoma (BAC) is a histological subtype of non-small cell lung cancer (NSCLC), particularly of adenocarcinoma. Given its multifocality and the poor activity of chemotherapy, there is no established treatment for BAC, although promising results have been achieved with inhibitors of the epidermal growth factor receptor (EGFR). No tumor marker has been validated in the diagnosis and follow-up of lung cancer, in particular to predict the outcome of treatment with EGFR inhibitors.Purpose As CA 15–3 antigen serum levels are reported to be pathologically abnormal in adenocarcinoma of the lung, we chose this tumor marker to monitor treatment with EGFR inhibitors of patients affected by adenocarcinoma with BAC features or pure BAC.Patients and methods We collected data from 26 consecutive Caucasian patients with BAC, mostly women and never smokers, who received EGFR inhibitors.Results We noticed that all patients with normal CA 15–3 serum levels at baseline (15/26, 57.7%) showed a response to EGFR inhibitors, whereas all patients with abnormal CA 15–3 serum levels (11/26, 42.3%) did not.Conclusion Our data suggest that CA 15–3 levels might be a predictive factor for the response to EGFR inhibitors in patients with BAC.

AbstractAngiosarcomas are rare soft tissue malignancies. Typically they originate from the skin of the scalp or face, whereas visceral sarcomas are very rare. We report the case of a 67-year-old man affected by a large angiosarcoma of the kidney. After surgical removal, a rapid peritoneal, visceral and cutaneous diffusion developed. Palliative chemotherapy, based on anthracycline and ifosfamide, which are normally used to treat all other high-grade spindle cell sarcomas, was totally inactive. On the basis of these results and of the biological characteristics of these rare neoplasms it is mandatory to develop other therapeutic approaches. Antiangiogenetic agents are of interest for this disease due to the peculiar origin of the cells of these sarcomas.

Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART).Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+T-cell counts (immunological non-responders), were selected from a prospective cohort study.After 1 year of HAART, 11 patients showed HIV viral load <2.6 log10cp/ml (virological responders), and 5 showed HIV viral load above this value (virological non-responders). Plasma samples, collected before starting therapy and after 1 year of HAART, underwent clonal sequence analysis for HVR-1 region of HCV. Non-synonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response.On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.

The prognostic role of GB virus type C (GBV-C) viraemia in HIV-infected subjects treated with highly active antiretroviral therapy (HAART) is still undefined, The aim of this analysis is to assess the relationship between GBV-C infection and response to antiretroviral therapy among HIV-infected subjects initiating HAART when antiretroviral-naive.A prospective, observational study of 400 HIV-infected patients with measurements of GBV-C RNA, hepatitis C virus (HCV) antibodies and HCV RNA determined from plasma stored prior to HAART initiation, Time to virological (achieving HIV RNA =500 copies/ml) and immunological success (a CD4+ count increase of =200cells/µl), and the time to virological relapse (confirmed HIV RNA >500 copies/ml) were assessed by Kaplan-Meier methods and Cox proportional hazard regression model.Of the subjects, 117 (29.3%) were GBV-C positive and, overall, 351 (87.8%) patients achieved virological success, After controlling for a number of confounders including HCV RNA, GBV-C viraemic patients experienced a significantly lower risk of HIV rebound than those who were GBV-C negative [relative hazard (RH)=0.56, 95% CI: 0.34–0.93, P=0.03], Conversely, the probability of achieving initial virological success or CD4+ count response after HAART did not differ between GBV-C-negative and -positive subjects, These results suggest that GBV-C coinfection may play a role in determining the rate of HIV rebound possibly by competing with HIV replication after HIV load has been successfully suppressed by HAART.

We examined the impact of a lamivudine-containing highly active antiretroviral therapy (HAART) regimen on 164 hepatitis B virus/HIV co-infected individuals starting their first HAART. Lamivudine-treated patients (accounting for 73% of the study population) showed a significantly lower level of alanine aminotransferase over follow-up [–81.1 mU/ml mean difference; 95% confidence intervals (95% CI): –30.3; –131.7, P=0.003] and a significantly reduced risk of liver-related morbidity/mortality [Relative hazard (RH)=0.07; 95% CI: 0.01–0.38, P=0.002] than those starting a lamivudine sparing-regimen.

High level HIV-1 drug resistance in recently infected treatment-naive individuals correlates with sub-optimal virological responses to highly active antiretroviral therapy (HAART). To determine whether genotypic HIV-1 drug resistance in chronic naive patients, as interpreted by various systems, could predict the virological outcomes of HAART, isolates from patients enrolled in a prospective observational cohort (ICoNA) prior to treatment start were genotyped. Genotypic susceptibility scores (GSS) assigned to the initial HAART regimens using the interpretations of pre-therapy resistance mutations by 13 systems were related to virological outcomes. Of 415 patients, 42 (10%) had at least one major resistance mutation. According to the different interpretations, 1.9–20.5% of patients had some level of resistance to at least one drug in the initial regimen. In multivariable analysis, GSS from two systems significantly predicted the time to virological success: Rega 5.5, for each unit increase in GSS adjusted relative hazard (RH) 1.86 [95% confidence intervals (95% CI): 1.15–3.02] and hivresistanceWeb v3, RH 1.87 (95% CI: 1.00–3.48). With three other systems, GSS showed a trend towards a significant prediction of success: Retrogram 1.6, RH 2.33 (95% CI: 0.98–5.53), Menéndez 2002, RH 2.36 (95% CI: 0.97–5.72) and Stanford hivdb, RH 2.06 (95% CI: 0.94–4.49). Genotypic resistance testing coupled with adequate interpretation in chronic naive patients can usefully identify those at risk of sub-optimal virological response to HAART.

We studied the predictive value of self-reported adherence and plasma drug concentrations on virological rebound to HAART. Among 238 participants in the AdICoNA study who had viral load =500 copies/ml, 42 (17.6%) experienced virological rebound by 96 weeks. Both self-reported non-adherence and sub-optimal concentration were independently associated with a higher risk of virological rebound.

To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma.

Incidence and mortality of AIDS patients have significantly declined in the developed countries due to the very active anti-HIV combination therapy available today. Because of the prolongation of the survival expectancy of these patients, other non-AIDS defining tumours have been recently reported in several cohort studies with increased frequency.

Summary A direct antiglobulin test (DAT) was performed in 70 patients with anti-HIV antibodies (group A: seropositive patients without or with minimal disease and group B: AIDS patients with or without malignancies). A positive DAT was found in 24 of 70 patients (34%, significantly higher compared to 0.1% in healthy controls) and a higher prevalence of positive DAT was observed in group B than in group A patients (55% versus 21% p<0.01). When comparing DAT-positive and negative patients within the same clinical group, no significant difference is seen in haemoglobin levels. There is no difference in serum bilirubin, haptoglobin or reticulocyte count between DAT-positive and negative patients altogether or in the same clinical group. AZT therapy seems to exert no significant influence on the onset of a positive DAT. The results confirm a high prevalence of positive DAT in patients with HIV antibodies, mainly in worse clinical conditions, and suggest that a positive DAT might be a prognostic factor in the clinical course of the disease.

Fifty cases of Hodgkin's disease in intravenous drug users (IVDU) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (G.I.C.A.T.). Ninety-two per cent of the patients were males; the median age was 26 years. Persistent generalized lymphadenopathy (PGL) at onset was present in 54% of patients, AIDS in 9%, ARC in 9% while 28% were simply HIV-positive. The initial median absolute number of CD4 lymphocytes was 264/mmc. Opportunistic infections were diagnosed in 20% of patients. In most patients the histological pattern was that of mixed cellularity and lymphocytic depletion (76%). In almost half the initial symptom was a persistent lymph node enlargement due to PGL. In the majority of patients (58%) only a clinical staging and bone marrow biopsy could be performed due to the presence of opportunistic infections, rapid disease progression or refusal of pathologic staging procedures. One patient presented with a Waldeyer's ring involvement, but no other unusual presentations were observed. After MOPP alternated or followed by ABVD or MOPP alone, 15/29 CR (52%) and 14/29 PR (48%) were observed. The median duration of CR was 14 months, while the median survival of CR has not been reached; the median survival of patients treated with chemotherapy with CD4 values at presentation {geq}400/mmc was significantly superior to that in those with CD4 < 400/mmc. The overall median survival was 16 months. Twenty-eight per cent of patients receiving chemotherapy + radiotherapy developed opportunistic as well as non-opportunistic infections (21%). Lethal hepatic toxicity was observed in 2 patients.In conclusion, Hodgkin's disease in IVDU was not found to be associated with unusual presentations, as previously reported for homosexuals. Complete remissions could be achieved in over 50% of patients, but in IVDU non-opportunistic infections in addition to opportunistic infections may also limit treatment administration. The presence of parenchymal functional impairment due to drug abuse, or drug abuse-related infections, such as pneumonia, endocarditis and hepatitis, should lead to the choice of antitumour agents with no or only minor potential liver, lung and cardiac toxicity.

Three patients with lung cancer (1 SCLC, 2 NSCLC) and pericardial malignant effusion received 100 mg/m2 Teniposide (VM 26) i.v. and, 1 week later, 50 mg/m2 intrapericardially. Plasma, pericardial, and urine levels of the drug were measured in all patients after the two treatments by a HPLC assay. After intrapericardial administration, a high VM 26 concentration was found in the pericardial cavity and slow systemic drug absorption was observed. Since the drug AUC after intrapericardial administration was approximately 15–21 times that after i.v. administration, it could be that this treatment is more effective against neoplastic deposits localized in the pericardium. Even though this small series does not permit conclusions to be drawn on the efficacy of VM 26 given intrapericardially, the lack of local toxicity, minimal systemic toxicity, and the response observed in two out of three patients given intrapericardial VM 26 suggest that further investigation should be carried out on this method of VM 26 administration.

The pharmacokinetics of 7-con-O-methylnogarol were investigated by HPLC assay with fluorometric detection in nine cancer patients with normal hepatic and renal function, after a 2-h infusion of 160 or 200 mg/m2. The drug disappeared from plasma biexponentially with a mean elimination half-life of 38±3 h; the mean apparent volume of distribution and the plasma clearance were 805±91 l/m2 and 14±2 l/h per m2. Within 48 h of administration, urinary excretion of the drug and its metabolite 7-con-O-methyl-N-demethylnogarol accounted for 2%–15% and 0.1%–6% of the dose, respectively. Neither 7-con-O-methylnogarol nor its N-demethyl derivative was conjugated with glucuronic acid or sulfate in detectable amounts.

In order to assess modes of human immunodeficiency virus (HIVV) transmission from heterosexual intravenous drug users (IVDUs) to their partners, condom use and sexual habits with both steady and occasional partners were investigated. A total of 349 heterosexual IVDUs (247 men and 102 women) who ignored, at the time of interview, their HIV serostatus were interviewed. Respondents were asked for information on condom use and sexual habits for the three year period prior to the interview. Nearly 40% of IVDUs reported sexual intercourse with both steady partners and occasional partners. Fifty-four percent of their steady partners and 48% of their occasional partners were individuals who did not belong to groups at risk for HIV infection. Anal intercourse with steady partners was reported by 29% of IVDUs and 24% of IVDUs with occasional partners. Condom use during vaginal intercourse was seldom reported: 83% of IVDUs never used a condom with steady partners and 75% did not use one with occasional partners. IVDUs who were 1) unmarried, 2) enrolled in the study after 1986, 3) partners of not at-risk individuals, 4) partners of a foreigner and, 5) aware of their partners HIV seropositivity showed significantly higher, albeit still low, frequencies of condom use with steady partners. Conversely, all these factors seemed to have little impact on condom use with occasional partners. Condom use and sexual habits were similarly reported by HIV-positive and HIV-negative IVDUs. The present study shows that high-risk sexual behaviours among IVDUs are very widespread and it stresses the need for intensive counselling to promote condom use among IVDUs.

In this phase III trial, 770 patients with clinical stage I-II Hodgkin's disease (HD) have been enrolled since November 1988. Preliminary results are given for the 605 (79%) patients who have completed their initial therapy. Patients were grouped according to 6 pretreatment prognostic characteristics. In the very favourable (VF) group, treatment consisted of mantle field alone. In the favourable (F) group, patients were randomized to either subtotal nodal irradiation (STNI), or 6 cycles of EBVP (epirubicin, bleomycin, vinblastine, prednisone) followed by; involved-field irradiation (IF-RT). Unfavourable (U) patients were randomized to either 6 cycles of EBVP plus IF-RT, or to 6 cycles of MOPP/ABV hybrid plus IF-RT.

In the EORTC lymphoma cooperative group, a randomized phase HI study was done for patients with stage II, III, IV intermediate- and high-grade lymphoma. Eight courses of CHVmP-VB were compared to eight courses of ProMACE-MOPP. Response was evaluated after 8 courses. Of 430 patients entered, 346 were eligible for this first analysis. Additional radiotherapy was given at initial large masses or residual disease after three courses.

Hodgkin's disease (HD) has been described in patients with HTV infection in association with unfavourable prognostic factors. Similarly, HD in the older general population has a poorer prognosis than in younger patients.

Older patients with non-Hodgkin's lymphoma (NHL) display a poorer response to chemotherapy and a significantly higher treatment-associated toxicity than do younger individuals. We investigated the potential clinical benefits and the cost-effectiveness of accelerated granulocyte recovery induced by recombinant granulocyte colony-stimulating factor (G-CSF) in patients with aggressive NHLs, aged 60–70 years, during treatment with a second-generation combination chemotherapy.

Ninety-two cases of Hodgkin's disease (HD) in patients with HIV infection have been collected by the Italian Cooperative Group on AIDS and Tumors (G.I.C.A.T.). In accordance with the epidemiology of HIV infection in Italy, 82% were intravenous drug users (IVDU), 8% homosexual men, 5% IVDU + homosexuals and 5% heterosexuals. At diagnosis of HD, 16% had AIDS, 20% AIDS related complex (ARC), 33% persistent generalized lymphadenopathy (PGL) and 31% were asymptomatic. Fifty-three percent of the patients had stage IV disease and 70% mixed cellularity and lymphocytic depletion. Forty-six patients were treated with MOPP or MOPP ≃ ABVD ± radiotherapy (zidovudine was not given) with complete remission (CR) in 54% and partial remission (PR) in 467percnt; of the patients. Fifty-six percent of these patients developed opportunistic infections (OI) during therapy or follow-up. Sixteen patients were treated with epirubicin, bleomycin and vinblastine (EBV) and concomitant zidovudine, with CR in 44% and PR in 38%. However, only one of these patients developed OI during therapy or follow-up. The clinico-pathological features and natural history of HD in HIV setting are peculiar and quite distinct from those observed in HD in the general population. Better combined chemotherapy and antiretroviral therapy is needed in order to ameliorate the CR rate and decrease the OI in patients with HIV infection and HD.

A multicentre cohort study was conducted in Italy to estimate the risk of developing AIDS in 261 intravenous drug users and 89 homosexual males for whom the seroconversion period was known.

A retrospective Eortc study was carried out in order to evaluate the incidence, clinico-pathoiogical findings and outcome of non-Hodgkin lymphoma and Hodgkin's disease in patients 70 years of age or older. A significant proportion of non-Hodgkin lymphoma, mostly with high-intermediate grade of malignancy occurs in these patients. Aggressive treatment, in particular chemotherapy with 3 drugs or more administered to elderly patients 70 years or older, median age 77 years, is associated with significant lethal and severe toxicity. Prospective randomized studies are clearly needed in order to evaluate the activity and the toxicity of intensive chemotherapy regimens specifically devised for patients aged 70 years or older with unfavourable non-Hodgkin lymphoma. Hodgkin's disease is unfrequently (5%) seen in patients 70 years of age or older. Mixed cellularity, B symptoms and stage III and IV account for 50, 47 and 47% of the cases respectively. Aggressive treatment is not associated with an increased lethal and severe toxicity compared with conservative treatment although 1 patient died of bone marrow toxicity after MOPP. Survival of patients 70 years or more with Hodgkin's disease seen in 1984 seems shorter than that in younger patients, especially due to high incidence of unfavourable prognostic factors, such as B symptoms and advanced stages.

in an Italian cooperative study on AIDS and cancer a diagnosis of Hodgkin's disease was established in 36 HIV-positive patients. the series was characterized by a high proportion of drug abusers, a high proportion of mixed cellularity and lymphocytic depletion subtypes and short survival. It is still unclear if HIV infection promotes the development of Hodghn's disease or only modifies the course of the disease. According to the authors, however, patients who are HIV seropositive and have biopsyproven Hodgkin's disease should be considered as fulfilling the criteria for AIDS.

Teniposide has been evaluated in a phase II clinical trial in chronic lymphocytic leukemia (CLL). Among 16 consecutive patients with CLL entered in the study and treated with Teniposide, 100 mg/m2 weekly, no objective response was observed. Toxicity was generally mild and mainly hematologic. Teniposide at this dosage and schedule is an inactive drug in CLL.

From February 1984 to February 1987, 29 patients with advanced, hormone-resistant prostatic carcinoma were treated with mitomycin-C at a dose of 20 mg/m2 every 6 weeks (15 mg/m2 in patients >75 years old and in those who had undergone previous radiotherapy). In the 27 evaluable patients, there were no complete remissions (CR), 2 partial remissions (PR), 14 stabilizations (STAB), and 11 cases of progressive disease (PRO). Ten stabilized patients showed significant pain reduction. Toxicity was minimal. The actuarial median survival was 10.8 months. In this study, mitomycin C was not active in terms of CR+PR; however, a beneficial symptomatic effect was frequently observed.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87), but the procedure carried considerable morbidity (7.5) and mortality (3.1). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

ObjectiveThe optimal therapeutic opproach for pts with HD-HIV is unknown, In an attempt to improve the results that we obtained in a previous prospective study with EBY without G-CSF (Cancer, 73: 437–44, 1994). in January 1993 we started a second trial consisting of CT, concomitant antiretroviral therapy (AZT or DDI), and G-CSF.