Treatment of early AIDS-related Kaposi's sarcoma with oral all-trans-retinoic acid: results of a sequential non-randomized phase II trial. Kaposi's Sarcoma ANRS Study Group. Agence Nationale de Recherches sur le SIDA

OBJECTIVE: To assess the efficacy and safety of all-trans-retinoic acid (ATRA), a retinoid with antitumour activity that inhibits in vitro the growth of Kaposi's sarcoma cells, in patients with low-risk AIDS-associated Kaposi's sarcoma. DESIGN: Non-randomized phase II study, using a group sequential procedure to determine whether the response rate to ATRA was above 10%. SETTING: Nine referral French centres. PATIENTS: Twenty HIV-seropositive men with CD4 cells > or = 200 x 10(6)/l, low-risk Kaposi's sarcoma [T0I0S0 according to the classification of AIDS Clinical Trials Group (ACTG)] not previously treated with systemic anti-Kaposi's sarcoma agents, and with at least four measurable lesions were included. INTERVENTIONS: ATRA was given orally 45 mg/m2 daily for 12 weeks. MAIN OUTCOME MEASURE: Tumour response evaluated according to ACTG criteria. RESULTS: Nineteen patients were evaluated for response: partial response, stabilization and progression were found in eight (42%), seven (37%), and four (21%) patients, respectively. Gradual flattening and lightening of lesions was observed in responders after at least 2 months of ATRA. All patients with partial response at week 12 pursued ATRA for another 15+/-7 weeks. Further improvement was observed in six patients. Median duration of response was 332 days. Cheilitis, transient headaches and skin dryness were the main toxicities noted. No significant changes in HIV viral burden or serum interleukin-6 pathways were observed. CONCLUSIONS: ATRA is well tolerated and effective enough in Kaposi's sarcoma patients to warrant further evaluation.     

A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's sarcoma

PURPOSE: The optimal dose of radiation in the treatment of AIDS-associated Kaposi's sarcoma has been controversial based on previous nonrandomized retrospective studies. METHODS AND MATERIALS: Seventy-one cutaneous AIDS-associated Kaposi's sarcoma lesions were randomly assigned to 1 of 3 radiation dose regimens--8 Gy in 1 fraction, 20 Gy in 10 fractions, and 40 Gy in 20 fractions. Lesions were measured prior to and following treatment. Complete resolution of palpable tumor was considered a complete response, regardless of residual purple pigmentation. Reduction in palpable tumor to less than 50% of pretreatment area was considered an objective response. Less than 50% reduction in tumor size was considered a nonresponse. RESULTS: Complete response was higher (p = .04) with 40 Gy (83%) and 20 Gy (79%) than with 8 Gy (50%). Absence of residual purple pigmentation was greater (p = .005) with 40 Gy (43%) than with 20 Gy (8%) or 8 Gy (8%). Lesion failure was lower (p = .03) with 40 Gy (52%) than with 20 Gy (67%) or 8 Gy (88%). Median time to failure was 43 weeks with 40 Gy, 26 weeks with 20 Gy, and 13 weeks with 8 Gy (p = .003). CONCLUSION: Fractionated radiotherapy to higher total doses resulted in improved response and control of cutaneous Kaposi's sarcoma. This dose-dependence should be considered in determining the optimal radiotherapeutic regimen for individual patients treated for epidemic Kaposi's sarcoma.     

The value of conventionally fractionated radiotherapy in the local treatment of HIV-related Kaposi's sarcoma

BACKGROUND: During the course of AIDS, 25 to 44% of homosexual patients infected with the human immunodeficiency virus develop Kaposi's sarcoma. Main manifestation is the skin. Response rates of 80 to 100% can be achieved with total dosage up to 50 Gy. Nevertheless, remissions can also be attained with 20 Gy of fractionated radiotherapy. As clinical data on low dose conventional fractionated radiotherapy are insufficient we analysed the response rates of an overall dose of 20 Gy in conventional fractionation. PATIENTS AND METHODS: From June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi's sarcoma of the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for skin and endoral lesions with a total reference dosage of up to 20 Gy. Side effects were assessed during therapy and the therapeutic result 6 weeks after end of treatment. RESULTS: Thirty-eight out of 111 lesions were judged as complete response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy. In 71/106 skin lesions (67%), radiation induced RTOG grade-1 reactions were observed. CONCLUSION: In patients with HIV associated Kaposi's sarcoma effective palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy in conventional fractionation. Yet, the fraction of patients with complete responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%). With reference to the reported data our results point to a dose-response relationship for Kaposi's sarcoma. Therefore higher total reference doses, e.g. 30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions, respectively, are suggested as by this mean the complete response rate can be doubled.     

Laryngeal Kaposi's sarcoma in patients with AIDS

Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.     

Re-treatment with interferon alfa of patients with chronic hepatitis C

Treatment of patients with chronic hepatitis C has had limited success because of relapses and nonresponse to interferon alfa therapy (currently the only established therapeutic agent). A retrospective study was done to determine the efficacy of re-treatment with interferon and the predictors of response in patients who failed to achieve sustained response after one standard course of interferon therapy (3 million units three times a week for 24 weeks). One hundred and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were included in the study. Eighteen relapsers and 13 nonresponders received a higher dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48 weeks) of interferon therapy. The remaining patients received the same regimen as the first treatment. Eighty-one percent and 23% of relapsers and nonresponders, respectively, had an end-of-treatment response, and 19% and 3% of the corresponding patient groups had a sustained response to re-treatment. Two patients with breakthrough during their first treatment were the only nonresponders with sustained response after re-treatment. Sustained response was observed only in patients who received an increased dose or duration of interferon therapy. No predictor of sustained response was found. In conclusion, sustained response to re-treatment with interferon was only observed with augmentation of dose or duration of therapy in some relapsers and patients who had breakthrough. Established predictors of response to interferon in naive patients, in particular serum hepatitis C virus RNA and genotype, were not associated with sustained response to re-treatment.     

Kaposi's sarcoma of the head and neck in patients with acquired immunodeficiency syndrome

Kaposi's sarcoma is the most common neoplastic process in patients infected with the human immunodeficiency virus. Moreover, the occurrence of Kaposi's sarcoma in human immunodeficiency virus-infected patients advances their classification to having the acquired immunodeficiency syndrome. We reviewed the medical records of 48 patients with human immunodeficiency virus infection who had Kaposi's sarcoma documented on their initial visit to the hospital. The onset of Kaposi's sarcoma occurred independent of the Centers for Disease Control and Prevention classification of human immunodeficiency virus infection (modified to exclude Kaposi's sarcoma). This neoplasm developed more frequently in patients who acquired human immunodeficiency virus infection by sexual contact (75% of cases), but manifestations were not significantly different in any of the risk populations for human immunodeficiency virus infection. Kaposi's sarcoma lesions were unpredictable and either showed progression, remained static, or occasionally, regressed spontaneously. Moreover, the lesions were usually multifocal at presentation, with the head and neck (62.5% of cases) as the primary site of involvement. In this region cutaneous lesions predominated (66.7%), followed by mucosal (56.7%) and deep structure (13.3%) involvement. The majority of patients with acquired immunodeficiency syndrome Kaposi's sarcoma involving head and neck structures were asymptomatic (80% of cases). Mucosal lesions were associated with symptoms in 29.3% of cases, whereas cutaneous lesions had symptoms in 5% of cases.     

Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group

PURPOSE: Cytotoxic chemotherapy is frequently required for the more severe manifestations of human immunodeficiency virus (HIV)-related Kaposi's sarcoma. Combinations of bleomycin and vincristine (BV) or BV with the addition of doxorubicin (ABV) are the most commonly used regimens against which new treatments may be compared. We report a multicenter phase III study that compared pegylated liposomal doxorubicin (PLD) to the BV combination. PATIENTS AND METHODS: We conducted a randomized study that compared PLD 20 mg/m2 with a combination of bleomycin 15 IU/m2 and vincristine 2 mg in 241 patients with HIV-related Kaposi's sarcoma. Both regimens were administered by intravenous infusion every 3 weeks for six cycles. RESULTS: A total of 121 patients received PLD and 120 patients the BV combination. The response to PLD was superior to BV: 58.7% versus 23.3% (P < .001). Patients who were randomized to receive BV, however, were more likely to terminate treatment early because of an adverse event (26.7% v 10.7%), and fewer completed the full six cycles of treatment (30.8% v 55.4%). Treatment with BV was associated with a significantly higher incidence of peripheral neuropathy (P < .001), whereas PLD treatment was more commonly associated with neutropenia and delays in receiving treatment (P < or = .001). CONCLUSION: Pegylated liposomal doxorubicin is an effective treatment for HIV-related Kaposi's sarcoma with a higher response rate than the BV combination. It is well tolerated but more myelosuppressive.     

Abnormalities of CD45 isoform expression in HIV infection

Systemic chemotherapy with 5-fluorouracil (5-FU) has been the mainstay of treatment for patients with metastatic colorectal carcinoma. Administering the drug in a continuous low-dose schedule has produced better result than bolus therapy. Resistance to short-pulse treatment can also be overcome by prolonged exposure. Recent studies suggest the feasibility of biomodulation of 5-FU with recombinant interferon (rIFN alpha-2a) with improved response. Sixteen patients were treated with continuous 5-FU 250 mg/m2 and rIFN alpha-2a 10 x 10(6) u thrice weekly for a maximum of 24 weeks. Five of them had received bolus 5-FU previously. Nine (82%) of the chemonaive group and 1 (20%) previously treated patient had partial response. The median duration of response was 7 months. Grade II to III mucositis were seen in 44% of the patients and 2 patients developed neurological complications. Although the overall response appeared encouraging, the incidence of toxicity was high. In the absence of further phase III studies, rIFN alpha-2a biomodulation of 5-FU cannot be regarded as standard treatment for patients with metastatic colorectal carcinoma.     

Diagnosis of pulmonary Kaposi's sarcoma by detection of human herpes virus 8 in bronchoalveolar lavage

Human herpes virus 8 (HHV8) DNA has recently been detected in sarcoma tissue of patients with Kaposi's sarcoma. HHV8 DNA could also be found in bronchoalveolar lavage (BAL) fluid of patients with tracheobronchial Kaposi's sarcoma. To determine the specificity, sensitivity and predictive values of HHV8 DNA detection in the BAL for the diagnosis of pulmonary Kaposi's sarcoma, 100 consecutive BAL were prospectively analyzed for the presence of HHV8 DNA using a nested PCR assay. In addition, 19 BAL samples of 14 AIDS patients with cutaneous or visceral Kaposi's sarcoma were retrospectively investigated. The prospective group consisted of 79 BAL performed in immunocompromised and of 21 BAL in nonimmunocompromised patients. Four patients of the prospectively analyzed group undergoing six BAL showed tracheobronchial Kaposi's sarcoma at five bronchoscopies. All of the five BAL samples performed in these patients with endoscopically visible Kaposi's sarcoma were positive for HHV8 DNA. Following chemotherapy and antiretroviral treatment tracheobronchial Kaposi's sarcoma was no longer detectable at a subsequent bronchoscopy and HHV8 DNA in BAL became negative in one patient. One BAL sample of a HIV-positive patient with no evidence of Kaposi's sarcoma was HHV8 DNA-positive. The sensitivity, specificity, positive and negative predictive values of HHV8 detection for the diagnosis of tracheobronchial Kaposi's sarcoma were 100%, 98.9%, 83.3%, and 100%, respectively. Twelve of 19 BAL samples of the retrospective group were HHV8 DNA-positive. In this group, 10 patients undergoing a total of 14 BAL suffered from pulmonary Kaposi's sarcoma. HHV8 DNA was documented in 10 of these 14 BAL samples. In three BAL of this group HHV8 DNA was positive, but pulmonary Kaposi's sarcoma was diagnosed at a later stage. In conclusion, the detection of HHV8 DNA in BAL is restricted to patients with Kaposi's sarcoma and is highly sensitive and specific for pulmonary involvement of Kaposi's sarcoma.     

Oligodendroglioma of the "widespread" type in the spinal cord

A phase II study of thalidomide was conducted to evaluate its efficacy and toxicity in the treatment of cutaneous AIDS-related Kaposi's sarcoma (AIDS-KS). To evaluate whether clinical response is correlated with titre of human herpesvirus 8 (HHV8) DNA in peripheral blood, levels were determined by serial end-point dilution at enrolment and 4-6 weeks later. Seventeen male HIV-seropositive patients with histopathologically diagnosed KS were treated with thalidomide 100mg orally once nightly for 8 weeks. Response evaluation was performed using AIDS Clinical Trials Group (ACTG) criteria and analysis was by intention to treat. Six of 17 patients achieved a partial response (35%: 95% confidence interval 10-61%). Eight patients withdrew (6 owing to toxicity, one to early progression and one to non-compliance). HHV8 DNA load decreased by at least 3log10 to undetectable levels in 3 of the 5 virologically assessable partial responders. This preliminary study demonstrates that thalidomide has activity in the treatment of AIDS-KS and that clinical response is associated with a reduction of HHV8 DNA titre in peripheral blood.     

The difficulties of treating infection in adults with cystic fibrosis

OBJECTIVE: Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy. DESIGN: Prospective study. PATIENTS: A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks. MEASUREMENTS: TSH and autoantibodies against thyroid were looked for at (-2) weeks and 24 weeks in all patients. Blood samples obtained at (-2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year. RESULTS: Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P < 0.001) antimicrosomal, antithyroglobulin, and/or anti-TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 1.5 years after interferon withdrawal. No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases. CONCLUSION: (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy; (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.     

The effects of spinal manipulation on the intensity of emotional arousal in phobic subjects exposed to threat stimulus: a randomized, controlled, double-blind clinical trial

DNA of HHV-8 (Kaposi's sarcoma-associated Herpes virus [KSHV]) was detected in a biopsy of a Kaposi's sarcoma in an elderly male patient from Saxony (East Germany). The diagnosis of classical Kaposi's sarcoma was first made in 1986. During World War II, the patient had been on active service on the Greek Islands of Crete and Rhodes only, he did not travel outside East Germany after the war. It is assumed that the patient was infected during his stay on the islands of Crete or Rhodes, where classical Kaposi's sarcoma is endemic. If so, the incubation period of classical Kaposi's sarcoma could be as long as 40 years.     

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.     

Distinct biology of Kaposi's sarcoma-associated herpesvirus from primary lesions and body cavity lymphomas

The DNA sequence for Kaposi's sarcoma-associated herpesvirus was originally detected in Kaposi's sarcoma biopsy specimens. Since its discovery, it has been possible to detect virus in cell lines established from AIDS-associated body cavity-based B-cell lymphoma and to propagate virus from primary Kaposi's sarcoma lesions in a human renal embryonic cell line, 293. In this study, we analyzed the infectivity of Kaposi's sarcoma-associated herpesvirus produced from these two sources. Viral isolates from cultured cutaneous primary KS cells was transmitted to an Epstein-Barr virus-negative Burkitt's B-lymphoma cell line, Louckes, and compared to virus induced from a body cavity-based B-cell lymphoma cell line. While propagation of body cavity-based B-cell lymphoma-derived virus was not observed in 293 cell cultures, infection with viral isolates obtained from primary Kaposi's sarcoma lesions induced injury in 293 cells typical of herpesvirus infection and was associated with apoptotic cell death. Interestingly, transient overexpression of the Kaposi's sarcoma-associated herpesvirus v-Bcl-2 homolog delayed the process of apoptosis and prolonged the survival of infected 293 cells. In contrast, the broad-spectrum caspase inhibitors Z-VAD-fmk and Z-DEVD-fmk failed to protect infected cell cultures, suggesting that Kaposi's sarcoma-associated herpesvirus-induced apoptosis occurs through a Bcl-2-dependent pathway. Kaposi's sarcoma-associated herpesvirus isolates from primary Kaposi's sarcoma lesions and body cavity-based lymphomas therefore may differ and are likely to have distinct contributions to the pathophysiology of Kaposi's sarcoma.     

Deduction: moving from the general to the specific

During a 29 month period, 46 patients with chronic hepatitis C virus (HCV) received recombinant human interferon alpha-2a for 6 months and were followed for another 6 months. The dose of interferon was three million units thrice weekly and was increased to six million units if amino transferase levels failed to return to normal after 2 months of therapy. At the end of the treatment 19 patients had a complete response, 6 had a near complete response, 2 patients had breakthrough during treatment, and the remaining 19 did not respond at all. Six months after treatment only 10 of the 19 responders remained in remission. Post-transfusion disease was associated with a significantly higher remission rate than sporadic disease (9/22 vs. 1/24, P < 0.001), as was also found in non-cirrhotic compared to cirrhotic patients (9/27 vs. 1/19, P < 0.001). Age, sex, duration of disease, serum aminotransferase, albumin, bilirubin, alkaline phosphatase, or Child's classification did not correlate with treatment response. Severe side effects necessitating cessation of treatment occurred in six patients, four of whom had major autoimmune phenomena. We conclude that careful selection of HCV patients with favorable response characteristics (post-transfusion etiology and non-cirrhotic liver) and without autoimmune manifestations can improve the remission rate and decrease the complication rate during interferon treatment.     

Concordance of common movement disorders among familial cases

A 51-year-old human immunodeficiency virus (HIV)-positive male patient (CDC stage 3C) had had a painful nodule on his external ankle joint for 10 months. A biopsy suggested bacillary angiomatosis, but Kaposi's sarcoma could not be excluded. Rods were detectable in lesional skin by a Warthin-Starry stain. A 298 base pair (bp) gene fragment specific for Bartonella species was amplified from lesional skin and direct nucleotide sequence analysis of the amplification product clearly identified Bartonella quintana. Kaposi's sarcoma-associated herpes virus specific DNA was not amplifiable by polymerase chain reaction (PCR) in our patient, suggesting that the lesion represented bacillary angiomatosis alone, despite clinical and histopathological features which suggested the coexistence of bacillary angiomatosis and Kaposi's sarcoma. The lesion regressed after erythromycin was prescribed. However, 4 and 9 weeks after initiation of therapy, PCR still yielded a positive result in material obtained by a swab. After complete healing, following 12 weeks of antibiotic therapy, PCR became consistently negative. The optimal length of antibiotic treatment in HIV-positive patients with bacillary angiomatosis is not yet known and inadequate therapy may be followed by disseminated disease and a fatal outcome. PCR-based monitoring of the success of treatment is valuable for determining the duration of treatment resulting in a cure.     

Interferon alpha-2b in the treatment of chronic hepatitis C: early experience

The antiviral and immunomodulatory effects of interferon were assessed in the treatment of chronic Hepatitis C in multi-ethnic patients to prevent viral replication and chronic liver damage. Three million units of recombinant interferon alpha-2b were administered three times a week for 48 weeks to a group of 9 active Hepatitis C patients. A clinical response was defined as normalization of serum ALT values. Serum was frozen and stored for Hepatitis C viral assays. Four patients normalized their liver functions. When viral levels were measured only two patients had unmeasurable levels of HCV RNA after treatment. Therapeutic results were observed and much work needs to be done to improve therapy because a serious epidemic is predicted for the future.     

Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study

We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma.     

Interferon antibodies in patients with chronic hepatitic C virus infection treated with recombinant interferon alpha-2 alpha

Patients treated with alpha-2a interferon for chronic hepatitis C may produce anti-interferon antibodies whose effect, if any, on the individual response to therapy has not been fully clarified. The prevalence and kinetics of anti-interferon, including those of neutralizing type, have been studied in 60 patients with chronic hepatitis C enrolled in a randomized controlled trial of recombinant alpha-2a interferon. Thirty patients received interferon while 30 were untreated controls. Two different methods, an enzyme immunoassay and an antiviral neutralization bioassay, were used and serial serum samples from each patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in 60.7% of treated patients within 6 months of therapy; antiviral neutralization bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay-positive patients, and was associated with high enzyme immunoassay reactivity and long-term persistence. Anti-interferon was detected in 75% of patients showing no response to interferon. Antibodies were also detected in three out of six patients who showed alanine aminotransferase normalization persisting up to the end of treatment and in 8 out of 14 patients who showed an initial marked reduction or even normalization of alanine aminotransferase, followed by reactivation of liver damage during treatment. Interestingly, patients who became anti-interferon positive before complete alanine aminotransferase normalization later showed reactivation of liver damage independently of interferon dose reduction, while patients who became positive for anti-interferon after complete alanine aminotransferase normalization either did not reactivate or did so only after interferon dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)