N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial.

BACKGROUND: Because of the single-agent activity of irinotecan hydrochloride, combination of irinotecan and docetaxel treatment against metastatic breast cancer (MBC) should be evaluated. PATIENTS AND METHODS: Single-stage phase 2 study of irinotecan and docetaxel to evaluate tumor response, toxicity, time to progression, and overall survival was carried out. Regimen of docetaxel (25 mg/m(2)) and irinotecan (70 mg/m(2)) was administered on days 1 and 8 of each 3-week cycle. Patients had histologically confirmed breast adenocarcinoma and metastatic cancer measurable with RECIST. RESULTS: Of 70 patients enrolled, 64 were assessable. Prior treatment with an anthracycline and a taxane was required. Eighteen (28%) patients [95% confidence interval (CI) 15% to 31%] had tumor response, plus four patients had stable disease (less than 30% decrease in sum of longest diameter and less than 20% increase) for >6 months. The clinical benefit rate was 34% overall. Median duration of tumor response was 6.7 months (95% CI 4.2-37.7 months); median follow-up was 18.6 months (range 8.5-37.7 months). The most common severe adverse events included fatigue [n = 16 (25%)] and neutropenia [n = 13 (20%)]. CONCLUSIONS: Weekly dosing of combination of irinotecan and docetaxel is active against MBC. However, the response rate to our regimen was not significantly better than single-agent docetaxel. Other schedules of irinotecan plus docetaxel should be considered for future studies.

A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer.

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled, double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1)) schedules (n=86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(-1) QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

Effect of treatment on health-related quality of life in acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma: a randomized trial of pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine.

The purpose of this study was to determine whether health-related quality of life (HRQL) would be improved in patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma treated by pegylated-liposomal doxorubicin (PLD) as compared to those treated by a conventional combination of doxorubicin, bleomycin, and vincristine (ABV). One hundred thirty-three patients received PLD and 125 patients received ABV every 2 weeks with a planned total of 6 cycles. Patients completed a 30-item AIDS-related HRQL questionnaire before beginning treatment (baseline), every 2 weeks while on treatment, and about 21 days after the end of treatment. Twenty-two items, involving nine domains, were analyzable. While on treatment, PLD-treated patients with partial clinical responses achieved statistically significant greater improvement (compared to baseline) in general health than did ABV-treated patients with partial clinical responses (rho = 0.008). By the end of treatment, the overall group of patients receiving PLD showed statistically significant greater improvement in pain and energy/fatigue than did the group receiving ABV (rho = 0.01-0.002). In addition, duration of clinically significant improvement in global QL was longer in the PLD arm.

Treatment of AIDS-related cutaneous Kaposi's sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group.

BACKGROUND: Kaposi's sarcoma (KS) is the most frequent malignancy in patients with HIV. Given the promise that retinoids show in the treatment of various hyperproliferative skin disorders and in vitro evidence of inhibition of proliferation of KS cells, a randomized, controlled clinical trial was conducted. METHODS AND RESULTS: A 12-week, multicenter, randomized, double-blind, vehicle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients. The primary efficacy endpoint was the patient's response rate, as determined by evaluating six index lesions representative of the patient's overall KS cutaneous disease using AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy. Of 268 patients entered in the blinded treatment phase of the study (alitretinoin group, n = 134; vehicle group, n = 134), 47 patients (35%) treated with alitretinoin 0.1% gel had a positive response, compared with 24 patients (18%) treated with vehicle gel. Of 184 patients receiving open-label alitretinoin treatment following the blinded phase of the trial, 90 patients (49%) met criteria for a positive response. This superior efficacy of alitretinoin gel over vehicle gel was maintained when the data were adjusted or analyzed for age, race, Kamofsky scores, baseline CD4+ lymphocyte counts, number of raised lesions at baseline, and aggregate area of index lesions. Alitretinoin 0.1% gel was superior to vehicle gel regardless of the number of concurrent antiretroviral therapies. Most adverse events were mild to moderate in severity, limited to the application site, and reversible on reduction in frequency or suspension of application. Relatively few patients (7%) discontinued alitretinoin therapy because of to related adverse events. CONCLUSIONS: The results show that alitretinoin gel application is safe and generally well tolerated, and they indicate the superiority of alitretinoin 0.1% gel over vehicle gel in the treatment of cutaneous AIDS-related KS lesions.

Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial.

PURPOSE: Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS). PATIENTS AND METHODS: Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes. RESULTS: Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin. CONCLUSION: Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.

Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.

To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.

Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

BACKGROUND: Reduced doses of cytotoxic chemotherapy or standard-dose therapy plus a myeloid colony-stimulating factor decreases hematologic toxicity and its complications in patients with non-Hodgkin's lymphoma associated with infection with the human immunodeficiency virus (HIV). However, the effect of reducing the doses of cytotoxic chemotherapeutic agents on clinical outcome is not known. METHODS: We randomly assigned 198 HIV-seropositive patients with previously untreated, aggressive non-Hodgkin's lymphoma to receive standard-dose therapy with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) along with granulocyte-macrophage colony-stimulating factor (GM-CSF; n=94) or reduced-dose m-BACOD with GM-CSF administered only as indicated (n=98). RESULTS: A complete response was achieved in 39 of the 94 assessable patients assigned to low-dose therapy (41 percent) and in 42 of the 81 assessable patients assigned to standard-dose therapy (52 percent, P= 0.56). There were no significant differences in overall or disease-free survival; median survival times were 35 weeks for patients receiving low-dose therapy and 31 weeks for those receiving standard-dose therapy (risk ratio for death in the standard-dose group=1.17; 95 percent confidence interval, 0.84 to 1.63; P=0.25). Toxic effects of chemotherapy rated grade 3 or higher occurred in 66 of 94 patients assigned to standard-dose therapy (70 percent) and 50 of 98 patients assigned to low-dose treatment (51 percent, P=0.008). Hematologic toxicity accounted for the difference. CONCLUSIONS: As compared with treatment with standard doses of cytotoxic chemotherapy (m-BACOD), reduced doses caused significantly fewer hematologic toxic effects yet had similar efficacy in patients with HIV-related lymphoma. Dose-modified chemotherapy should be considered for most HIV-infected patients with lymphoma.

Mitoguazone therapy in patients with refractory or relapsed AIDS-related lymphoma: results from a multicenter phase II trial.

PURPOSE: Patients with AIDS-related lymphoma usually have extensive lymphomatous disease, with relatively frequent involvement of the CNS. Approximately half may achieve complete remission after chemotherapy. Mitoguazone, an inhibitor of polyamine biosynthesis, has demonstrated efficacy in patients with de novo recurrent lymphoma. The drug is relatively nonmyelotoxic and may cross the blood-brain barrier. The current study was designed to assess the safety and potential efficacy of mitoguazone in patients with relapsed or refractory AIDS-lymphoma. PATIENTS AND METHODS: Thirty-five patients were accrued, all of whom had failed one (51%) or multiple (two to six) prior regimens. Mitoguazone (600 mg/m2) was given intravenously on days 1 and 8, and then every 2 weeks, until best response, progression, or toxicity. RESULTS: The median age was 39 years. High-grade lymphoma was diagnosed in 29 patients (83%). Extranodal disease was present in 30 patients (86%), with multiple extranodal sites (two to seven) in 18 (51%). The median CD4 cell count at study entry was 66/dL (range, zero to 549). Twenty-six patients were assessable for response. The objective response rate was 23% (95% confidence interval [CI], 6.9 to 39.3), with complete remission in three patients (11.5%), and partial remission (PR) in three patients (11.5%). Six patients experienced stable disease. Median survival from study entry was 2.6 months for the group as a whole; 21.5 months (range, 3.8 to 29.1) in complete responders, 5.6 months (range, 3.8 to 34.8) in partial responders. The most common toxicities occurred solely during drug infusion and included vasodilation (63%), paresthesia (86%), and somnolence (17%). Fourteen patients (40%) experienced nausea and 16 (46%) vomiting (grade 3 in one). Ten patients (29%) developed stomatitis, including grade 3 in two and grade 4 in one. Seven patients (20%) developed neutropenia, with grade 4 in one. Thrombocytopenia occurred in nine patients (26%). While on study, three patients developed sepsis, four had pneumonia, and two developed opportunistic infections. CONCLUSION: Mitoguazone is an effective agent in patients with multiply relapsed or refractory AIDS-related lymphoma, with acceptable toxicity. Further study in patients with newly diagnosed disease is warranted.

Population pharmacokinetics and pharmacodynamics of pegylated-liposomal doxorubicin in patients with AIDS-related Kaposi's sarcoma.

OBJECTIVE: To characterize the population pharmacokinetics of pegylated-liposomal doxorubicin in patients with acquired immunodeficiency disease (AIDS)-related Kaposi's sarcoma and to explore the relationship between response of the cutaneous Kaposi's sarcoma lesions to treatment and measures of drug exposure. METHODS: Forty-three male patients (median age, 40 years; age range, 28 to 50 years), body surface area, 1.89 m2; range, 1.5 to 2.3 m2) with AIDS and at least five biopsy-proven cutaneous Kaposi's sarcoma lesions were randomized to receive either a 10 or 20 mg/m2 dose of study drug for their first cycle and the alternate dose 3 weeks later. Patients continued to receive the study drug at a dose of 20 mg/m2 every 3 weeks. Serial blood samples were obtained after the first two doses and analyzed by HPLC for determination of total plasma doxorubicin concentration. Kaposi's sarcoma lesion response was categorized as either progressive disease, stable disease, partial response, or complete response. Classification and regression tree (CART) analysis was used to determine the relationship between drug exposure and categorical lesion response. Iterative two-stage analysis was used to characterize both the pharmacokinetics of pegylated-liposomal doxorubicin and to model the probabilities of achieving a specific lesion response. RESULTS: The pharmacokinetics of pegylated-liposomal doxorubicin were best described by a two-compartment linear structural model. Lesion response was significantly related to both the average daily maximum doxorubicin concentration (Cmax,avg) and dose intensity. CONCLUSIONS: The pharmacokinetics of pegylated-liposomal doxorubicin are strikingly different from conventional doxorubicin. Identification of both Cmax,avg and dose intensity as predictors of lesion response will provide guidelines for future dosing regimen designs.

Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma after failure of standard chemotherapy.

PURPOSE: To determine the efficacy and safety of pegylated-liposomal doxorubicin in patients with AIDS and Kaposi's sarcoma (AIDS-KS) who experienced failure of standard chemotherapy. METHODS: Fifty-three patients with advanced AIDS-KS who experienced disease progression or intolerable toxicities while receiving standard doxorubicin/bleomycin/vincristine (ABV) or bleomycin/vincristine (BV) chemotherapy were identified from a cohort of patients who were then treated with pegylated-liposomal doxorubicin. Patients received 20 mg/m2 pegylated-liposomal doxorubicin (Doxil; Sequus Pharmaceuticals, Inc, Menlo Park, CA) every 3 weeks. RESULTS: Nineteen patients (36%) had a partial response (PR) and one patient had a clinical complete response (CCR). The median duration of response and time (from study entry) to treatment failure were 128 and 134 days, respectively. Of 28 patients who experienced disease progression while receiving combination regimens that contained standard doxorubicin, the PR rate was 32%, which suggests that the pegylated-liposomal encapsulation increases the therapeutic effect of doxorubicin. Patients obtained clinical benefits such as flattening of lesions (48%), improved lesion color (56%), relief of pain (45%), and loss of edema (83%). Forty-nine percent of patients had more than one clinical benefit. The most common adverse effect was leukopenia, which occurred in 40% of patients. Only 15% of patients had nausea and/or vomiting, none of which was severe; 9% experienced alopecia, also generally mild. CONCLUSION: Pegylated-liposomal doxorubicin offers a new alternative for treatment of patients who have experienced failure of standard chemotherapy for AIDS-KS.

Anal neoplasia. Pathogenesis, diagnosis, and management.

Prolonged, severe immunodeficiency provides the necessary milieu for the emergence of anogenital neoplasia caused by human papillomaviruses. Anal neoplasia is likely to become a more common manifestation of HIV disease as patients with profound immunodeficiency, who would have succumbed to opportunistic infections earlier in the epidemic, are now surviving for extended periods of time because of increasingly effective antiretroviral, prophylactic, and antimicrobial therapies. The screening and treatment strategies described for use in HIV-infected patients with anal neoplasia are currently being investigated and refined.

Anal neoplasia in persons with HIV infection.

AIDS: Aside from the neoplasms that are clearly related to immunodeficiency, such as non-Hodgkin's lymphoma and Kaposi's sarcoma, numerous observations have also shown an association between HIV infection and the incidence of cervical and anal neoplasms. Human papillomavirus (HPV) is the etiologic factor in anogenital neoplasms, although the mechanisms of the association are not clearly understood. It is believed that several HPV genes are critical in the malignant cell transformation process. An etiologic similarity exists between cervical and anal neoplasms, and the risk factors for the former appear to be the same for the latter, such as history of anal or genital warts, history of sexually transmitted diseases (STDs), and certain sexual practices. In addition, a number of studies have shown a relation between HIV-induced immunodeficiency, HPV infection, and the development of anal neoplasms. In a study of 210 men, anal intraepithelial neoplasia was more common in HIV-infected patients than non-HIV-infected patients. Additional risk factors for abnormal cytology included CD4 count under 200, and a history of smoking. Patients who receive surgical treatment for anal carcinoma have been shown to have poor outcome and short survival. Standard treatments, including ablation, surgery plus radiotherapy for small localized lesions, and radiotherapy plus chemotherapy, are preferable for anal neoplasia. Due to the increasing incidence of HPV infection as a manifestation of HIV disease, strategies for screening and treating these patients must be refined.^ieng

Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma.

A study of the plasma pharmacokinetics, tumor localization, and safety of a single dose of doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol (PEG-liposomal doxorubicin) was conducted in patients with Kaposi's sarcoma (KS) as a manifestation of acquired immune deficiency syndrome (AIDS). Eighteen patients with AIDS-KS diagnosed by examination of biopsy specimens were randomly assigned to receive either standard doxorubicin or PEG-liposomal doxorubicin. Consecutive participants were entered at three dose levels (10, 20, and 40 mg/m2) in ascending fashion. Clearance of PEG-liposomal doxorubicin was 0.034 L/h/m2 to 0.108 L/h/m2, volume of distribution (Vd) was 2.2 L/m2 to 4.4 L/m2, and half-lives (t1/2) of the initial decline in the plasma concentration-time curve and of the terminal decline were 3.77 hours and 41.3 hours, respectively. Seventy-two hours after administration, doxorubicin levels observed in lesions of patients receiving PEG-liposomal doxorubicin were 5.2 to 11.4 times greater than those found in patients given comparable doses of standard doxorubicin. PEG-liposomal doxorubicin and standard doxorubicin were roughly equipotent in producing toxicity. Encapsulation in liposomes containing surface-bound PEG significantly limits the distribution and elimination of doxorubicin, results in greater accumulation of the drug in KS lesions 72 hours after dosing than does standard doxorubicin, and may improve drug efficacy and therapeutic index in the treatment of AIDS-KS.

Malignant germ cell tumors in men infected with the human immunodeficiency virus: natural history and results of therapy.

PURPOSE: To determine how men infected with the human immunodeficiency virus (HIV) tolerate and respond to treatment for malignant germ cell tumors (GCTs), and how GCT histology and stage compare among HIV-infected versus non-HIV-infected men. PATIENTS AND METHODS: Two hundred ninety-four cases of GCT diagnosed or treated from 1980 to 1993 were reviewed. Nine new cases among HIV-infected men were identified; these were analyzed together with six cases previously reported from our institution. RESULTS: Low-stage tumors (stages I and IIA) comprised 67% of HIV-infected and 63% of non-HIV-infected cases. Sixty-seven percent of HIV-infected cases were seminomas versus 51% of non-HIV-infected cases. Ten patients had AIDS at the time of GCT diagnosis. Five patients underwent radiation therapy and one patient underwent retroperitoneal lymphadenectomy without complications. Seven patients received chemotherapy with four cycles of cisplatin, etoposide, and bleomycin (PEB) or cisplatin, vinblastine, and bleomycin (PVB) without excess cytopenias or new opportunistic infections. Of seven patients treated for advanced disease, there were five complete and two partial responses. Six patients have died of AIDS at a median of 20 months after diagnosis of GCT. The median follow-up time for surviving patients has been 42 months (range, 8 to 87) and all but one remain without evidence of active disease. In no case was a patient's HIV disease classification altered by antitumor therapy. CONCLUSION: The natural history of GCTs is comparable in HIV-infected and non-HIV-infected men and standard therapy including orchiectomy, retroperitoneal lymph node dissection, radiation therapy, and chemotherapy is well tolerated.

Outcome for hospitalized patients with fever and neutropenia who are infected with the human immunodeficiency virus.

We conducted a retrospective cohort study to evaluate the occurrence of bacteremia and associated mortality among hospitalized patients who were seropositive for the human immunodeficiency virus (HIV) and who developed fever and neutropenia following antineoplastic chemotherapy or for other reasons. Review of medical records revealed 224 episodes in 142 patients. Of these episodes, 57% occurred following antineoplastic chemotherapy, and 43% occurred under other circumstances. Members of the chemotherapy group had significantly less-advanced HIV disease, a lower mean absolute-neutrophil-count nadir, and a shorter duration of hospitalization. There was no difference between the two groups in the frequency of bacteremia or mortality due to all causes when they were compared by multivariate analysis. Statistically significant univariate and multivariate predictors of bacteremia included sepsis syndrome and concurrent infection. Predictors of mortality included sepsis syndrome, concurrent infection, bacteremia, and antimicrobial therapy. This study suggests that the cause of neutropenia in HIV-seropositive patients is not a predictor of the outcome of fever and neutropenic episodes. Instead, clinical presentation and concomitant illnesses have a greater impact on outcome for a patient.

Continuous low-dose interferon-alpha therapy for HIV-related immune thrombocytopenic purpura.

Our objective was to examine the efficacy and toxicity of continuous, low-dose interferon-alpha therapy for human immunodeficiency virus-related immune thrombocytopenic purpura (HIV-ITP) in a Phase II clinical trial overseen by a community-based consortium of physicians conducting clinical trials in HIV-related diseases. Sixteen patients with HIV-ITP defined by prospective clinical criteria were enrolled; the majority had failed other therapies for HIV-ITP. Baseline and serial measurements were made of platelet counts, complete blood counts, serum chemistries, platelet-associated immunoglobulin, and CD4+ T-lymphocyte counts; subjective symptoms and bleeding were recorded. Three million units of interferon-alpha 2b were self-administered by subcutaneous injection every Monday, Wednesday, and Friday for 16 weeks. Thirteen participants were evaluable for response. One obtained a complete response, eight had partial responses, and four had no response to interferon-alpha therapy. The mean absolute platelet count of the group rose from 15.5 x 10(9)/L at baseline to 47.3 x 10(9)/L at 2 weeks and remained in this range for the duration of the study. CD4+ T-lymphocyte counts and serum chemistries did not change significantly during therapy. Ability to detect platelet-associated immunoglobulin did not change in a predictable manner in relation to platelet count response. Hematologic toxicity was limited to one episode of granulocytopenia, which resolved after a lowering of zidovudine dosage. Subjective toxicities were mild and tolerable, and minor bleeding problems improved in all participants so affected. Low-dose, continuous therapy with interferon-alpha resulted in meaningful increases in the platelet counts of the majority of study participants with HIV-ITP. Interferon-alpha was safe and tolerable for most participants with HIV-ITP at the dosage and schedule employed in this study. Interferon-alpha for clinically significant thrombocytopenia and who have failed to respond to zidovudine.

Treatment of Kaposi's sarcoma. Current guidelines and future perspectives.

Kaposi's sarcoma is the most common malignancy associated with HIV infection, and the morbidity and mortality attributable to AIDS-related Kaposi's sarcoma (AIDS-KS) may be increasing. No curative therapy is available for AIDS-KS, but palliative therapy can eliminate or reduce cosmetically unacceptable lesions, reduce painful or unsightly oedema or lymphadenopathy, shrink symptomatic oral lesions and relieve symptoms caused by visceral involvement. Strategies currently employed to treat the various clinical problems encountered in AIDS-KS include single- and multi-agent cytotoxic chemotherapy, treatment with interferon-alpha, radiotherapy, and other local therapies. Current clinical research is focusing on use of liposome-encapsulated cytotoxic agents and treatment with substances that inhibit angiogenesis. Any treatment plan for AIDS-KS must be flexible and must be based on the patient's overall clinical and immunological status as well as therapeutic goals. Limited local disease is usually amenable to treatment with local measures. Extensive, symptomatic AIDS-KS warrants systemic treatment. The response of mucocutaneous lesions to low dose systemic cytotoxic chemotherapy is typically excellent. Treatment with interferon-alpha may also be beneficial in this setting. Multi-agent chemotherapeutic regimens are usually reserved for treatment of patients most severely affected by AIDS-KS. It is hoped that liposome-encapsulated cytotoxic chemotherapy and antiangiogenic therapies will prove more effective and less toxic than the treatment strategies currently in use.