A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer.

BACKGROUND: Continuation or 'switch' maintenance therapy is commonly used in patients with advancd non-small-cell lung cancer (NSCLC). Here, we evaluated the efficacy of the telomerase inhibitor, imetelstat, as switch maintenance therapy in patients with advanced NSCLC. PATIENTS AND METHODS: The primary end point of this open-label, randomized phase II study was progression-free survival (PFS). Patients with non-progressive, advanced NSCLC after platinum-based doublet (first-line) chemotherapy (with or without bevacizumab), any histology, with Eastern Cooperative Oncology Group performance status 0-1 were eligible. Randomization was 2 : 1 in favor of imetelstat, administered at 9.4 mg/kg on days 1 and 8 of a 21-day cycle, or observation. Telomere length (TL) biomarker exploratory analysis was carried out in tumor tissue by quantitative PCR (qPCR) and telomerase fluorescence in situ hybridization. RESULTS: Of 116 patients enrolled, 114 were evaluable. Grade 3/4 neutropenia and thrombocytopenia were more frequent with imetelstat. Median PFS was 2.8 and 2.6 months for imetelstat-treated versus control [hazard ratio (HR) = 0.844; 95% CI 0.54-1.31; P = 0.446]. Median survival time favored imetelstat (14.3 versus 11.5 months), although not significantly (HR = 0.68; 95% CI 0.41-1.12; P = 0.129). Exploratory analysis demonstrated a trend toward longer median PFS (HR = 0.43; 95% CI 0.14-1.3; P = 0.124) and overall survival (OS; HR = 0.41; 95% CI 0.11-1.46; P = 0.155) in imetelstat-treated patients with short TL, but no improvement in median PFS and OS in patients with long TL (HR = 0.86; 95% CI 0.39-1.88; and HR = 0.51; 95% CI 0.2-1.28; P = 0.145). CONCLUSIONS: Maintenance imetelstat failed to improve PFS in advanced NSCLC patients responding to first-line therapy. There was a trend toward a improvement in median PFS and OS in patients with short TL. Short TL as a predictive biomarker will require further investigation for the clinical development of imetelstat.

A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.

BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.

Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.

BACKGROUND: We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression. RESULTS: Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup. CONCLUSIONS: This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. ClinicalTrials.gov identifier: NCT00902291.

Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center.

The reported experience with Hodgkin's disease (HD) in the United States has come primarily from large referral centers that attract a predominantly white population of high socioeconomic status (SES). The majority of these patients had the nodular sclerosis (NS) histologic subtype and asymptomatic stage I/II disease. We have reviewed the records of 178 patients with HD seen within the past 17 years at Los Angeles County-University of Southern California Medical Center (LAC/USC), which is a nonreferral, government-operated facility. Our patient population was found to be heterogeneous, with 38% white, 22% black, and 36% Hispanic. Systemic "B" symptoms were noted in 62% of patients at diagnosis, and 63% had advanced disease (stage III or IV). NS pathologic subtype was present in only 52% of the group. Comparison between the races revealed: (1) Hispanics had a higher incidence of lymphocyte depleted subtype and less NS than whites (P less than .06); (2) whites had equal distribution between stages I/II and III/IV; (3) blacks and Hispanics presented more frequently with stage III/IV (P = .10); and (4) extranodal involvement occurred most often in bone in whites, and was equally distributed between liver, lung, and bone in blacks and Hispanics. We conclude that the lower SES, mixed racial population seen at our institution more closely resembles the reports of HD in Third-World countries and is characterized by advanced symptomatic disease. Further, the clinical pathologic characteristics of HD in the United States may vary significantly, depending upon the precise ethnic and socioeconomic status of the patients being served.

AIDS-related malignant lymphoma: results of prospective treatment trials.

Twenty-two consecutive patients with high-grade, B-cell lymphomas related to the acquired immunodeficiency syndrome (AIDS) were accrued onto two sequential phase II studies, consisting of a standard regimen (M-BACOD, group no. 1, N = 13), or a novel, intensive regimen (group no. 2, N = 9), which included high-dose cytosine arabinoside (HD-Ara-C), and high-dose methotrexate (HD-MTX), in an attempt to prevent CNS relapse and improve response rates. Stage IV disease was present in 82%. Complete remission (CR) was achieved in seven of 13 patients (54%) in group no. 1, and in three of nine (33%) group no. 2 (P = NS). By multivariate analysis, the most significant factor in predicting response was a Karnofsky performance score (KPS) greater than 60 (P = .04). Three of the ten patients who achieved CR on either regimen have relapsed; in all, five of 13 patients (31%) in group no. 1 have achieved disease-free survival for more than 1 year, compared with one of nine (11%) in group no. 2. CNS progression occurred in six patients in group no. 2, and in two patients in group no. 1. Hematologic toxicity was significantly greater in group no. 2, and these patients had an increased risk of opportunistic infection (one in group no. 1 v seven in group no. 2; P less than .01). Survival was similar, with a median of 11 months in group no. 1 and 6 months in group no. 2. We conclude that the intensive regimen of combination chemotherapy described here is associated with significant risk of early death due to opportunistic infection in patients with AIDS-related lymphoma, and that progression in the CNS remains a major problem. Trials of combination chemotherapy of a less intensive nature, perhaps in combination with immunomodulators or antiretroviral agents should be explored.

Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma.

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

Human T-cell lymphotropic virus type III associated disorders. The spectrum in the heterosexual population.

Eleven heterosexual patients (nine women, two men) without classic risk factors for development of acquired immunodeficiency syndrome (AIDS) were seen between March 1983, and April 1985, and diagnosed as having AIDS (four), persistent, generalized lymphadenopathy (PGL) (four), or asymptomatic human T-cell lymphotropic virus type III (HTLV-III) carrier state (three). The clinical presentations and course of those with AIDS or PGL were similar to those reported in homosexual men with AIDS or PGL, with reversed T4/T8 ratio, and the presence of antibody to HTLV-III. Asymptomatic carriers had normal T4/T8 ratios, had an absence of HTLV-III antibodies, but had HTLV-III virus cultured from blood. We conclude that the heterosexual population, with or without history of sexual exposure to individuals at risk for AIDS, may develop a wide range of clinical manifestations secondary to HTLV-III, varying from AIDS to the asymptomatic carrier state.

Treatment of a unique anemia in patients with IDDM with epoetin alfa.

OBJECTIVE: To identify and treat a unique form of anemia in patients with long-term IDDM. RESEARCH DESIGN AND METHODS: Patients with IDDM, unexplained symptomatic anemia, and serum creatinine levels of < 177 mumol/l (2.0 mg/dl) were treated with epoetin alfa (Procrit, Ortho Biotech, Raritan, NJ), 50 U/kg three times weekly, subcutaneously, to reach a target hematocrit of 38-40%. Baseline serum erythropoietin titers were measured before drug therapy. RESULTS: Six patients were treated with epoetin alfa. Median age of the group was 74 years, with IDDM being diagnosed for a median of > 20 years. All patients had symptoms of anemia with a median hematocrit of 28.9% (range 27-31). Compared with iron deficiency control patients, the group had a limited erythropoietin (EPO) response to the degree of anemia. All patients showed increases in hematocrit, median peak of 40.9%, with median time-to-peak response of 12 weeks. Baseline symptoms of anemia resolved in all patients. No adverse effects were noted during the treatment period. CONCLUSIONS: There is a unique form of anemia in patients with long-term IDDM and clinically normal renal function who respond to low-dose epoetin alfa therapy. The rapid response to therapy and depressed baseline erythropoietin titers suggest the anemia is due to a lack of endogenous EPO release.

The long-term use of zidovudine in patients with severe immune-mediated thrombocytopenia secondary to infection with HIV.

Various treatments for HIV-related thrombocytopenia have been reported. Since etiologies of the thrombocytopenia may differ with regard to risk group treatment outcomes may also vary. We have recently studied the long-term use of zidovudine in individuals with sexually transmitted HIV infection and severe thrombocytopenia. Twenty-five men, median age 34 years (range, 23-51 years), were treated with zidovudine (1000 mg/day) for a median duration of 12 months (range, 2.5- less than 26 months). Nineteen patients (76%) had had episodes of symptomatic bleeding secondary to thrombocytopenia prior to study entry. All patients bleeding symptoms resolved with therapy. Six (24%) achieved a complete response, with normalization of platelet counts, while 11 patients (44%) achieved a partial response, giving an overall response rate of 68%. The median time to partial or complete normalization of platelet counts was 12 weeks (range, 4-62 weeks). Toxicities were minimal during the study period. Only one patient developed an AIDS-defining diagnosis while on therapy. We conclude that patients with sexually transmitted HIV infection and immune thrombocytopenia may need a prolonged period of therapy with zidovudine to achieve a platelet response. Other treatment modalities may be required for the 30% of patients who do not respond to zidovudine.

Seronegative disseminated coccidioidomycosis in patients with HIV infection.

Serologic testing for complement-fixing antibodies to Coccidioides immitis is commonly employed to assist in the diagnosis and management of this infection, but its usefulness in an HIV-coinfected population is unknown. In this study we reviewed all the mycologically or histologically proven cases of disseminated C. immitis infection after 1982. Disseminated C. immitis and proven HIV infection were present in eight patients. We performed serum complement-fixing antibody titers on all eight patients, six of whom gave positive tests, while two patients (25%) gave repeatedly negative results despite widely disseminated disease. We conclude that histopathology and culture remain the most reliable methods for the diagnosis of disseminated coccidioidomycosis in the HIV-infected host.

Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma.

OBJECTIVE: To determine the maximum tolerated dose of granulocyte-macrophage colony-stimulating factor (GM-CSF) that would reduce the severity and duration of neutropenia from combination cytotoxic chemotherapy in the treatment of AIDS-related Kaposi's sarcoma (KS). DESIGN: Phase I, dose escalation. SETTING: Outpatient clinic of a university hospital. PATIENTS: HIV-seropositive patients with advanced KS. INTERVENTIONS: Combination chemotherapy consisting of adriamycin, bleomycin, and vincristine (ABV), with escalating doses of recombinant human GM-CSF (rhGM-CSF). Patients were treated for a median of six cycles (range, between two and seven cycles) of biweekly chemotherapy with GM-CSF administered in divided daily subcutaneous doses on days 2-12. Serum cytokine levels of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured before, during, and after therapy to correlate with response to therapy. RESULTS: A GM-CSF dose of 250 micrograms/m2 was well tolerated, whereas the next dose escalation, of 500 micrograms/m2, was associated with dose-limiting toxicities, including grade 3 fever, fatigue, and diarrhea. GM-CSF produced predictable cyclic increases in granulocytes, allowing for delivery of full-dose chemotherapy on schedule. All patients were HIV-p24-antigen-negative at study entry; no activation of p24 antigenemia was observed after repeat testing. Consistent changes in cytokine levels were not observed. Responses included one complete and three partial responses, and two patients with stable disease parameters. CONCLUSIONS: We conclude that GM-CSF can be administered safely to patients with AIDS-related KS receiving myelosuppressive chemotherapy, resulting in granulocytic response, without up-regulation of HIV p24 antigen levels in serum.

The use of fine needle aspiration cytology in the management of human immunodeficiency virus-related non-Hodgkin's lymphoma and Hodgkin's disease.

We prospectively studied the utility of fine needle aspiration (FNA) to diagnose non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) in patients with human immunodeficiency virus (HIV) infection and lymphadenopathy. Twenty-one patients with a clinical evidence of lymphoma underwent 24 FNA and site-specific tissue biopsies. Twenty-two of the 24 biopsy results were consistent with a malignant lymphoproliferative neoplasm: NHL (19 cases), HD (two cases), and T-cell lymphoma (one case). Two biopsies showed reactive lymphoid hyperplasia consistent with a clinical diagnosis of persistent generalized lymphadenopathy. There was an 87% correlation (21 of 24) between FNA and biopsy diagnoses. Eighteen of the 19 biopsy-confirmed NHL cases were diagnosed with FNA. Both cases of HD and the one T-cell lymphoma were also diagnosed with aspirate material. In conclusion, the FNA in HIV-infected individuals with suspected malignant lymphadenopathy is highly sensitive (95%). The FNA, when used in conjunction with the clinical appearance, is a useful tool in the management of HIV infection and lymphadenopathy.

Phase I trial of m-BACOD and granulocyte macrophage colony stimulating factor in HIV-associated non-Hodgkin's lymphoma.

The use of full-dose intensive regimens of chemotherapy in patients with HIV-associated lymphoma has often resulted in severe toxicity, treatment delay, and reduced subsequent dosing. We conducted a Phase I trial to evaluate the toxicity of the combination of m-BACOD (methotrexate, Bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) with granulocyte-macrophage colony stimulating factor (GMCSF) in these patients. A total of 17 patients were entered and treated at three dose levels of m-BACOD in combination with a fixed dose of GMCSF. Eight patients received standard dose m-BACOD plus GMCSF without experiencing dose-limiting hematologic toxicity, although significant nonhematologic toxicity was seen. We conclude that it is feasible to treat patients with HIV-associated lymphoma using standard dose m-BACOD plus GMCSF, but further study is needed to determine whether full-dose regimens improve survival when compared with reduced dose regimens in these individuals.

Serum erythropoietin titers in patients with human immunodeficiency virus (HIV) infection and anemia.

The pathophysiology of anemia in patients with human immunodeficiency virus (HIV) infection is multifactorial. In order to determine the role of erythropoietin (EPO) response as a cause of the anemia, serum levels were determined by direct radioimmunoassay in 110 symptomatic patients with various stages of HIV infection. Symptomatic patients (ARC and AIDS) not receiving zidovudine (ZDV) therapy demonstrated a strong inverse relationship between serum EPO and hemoglobin levels (p = 0.01 and p less than 0.001, respectively). Patients with AIDS who were anemic while receiving ZDV demonstrated serum EPO levels that ranged from normal to markedly elevated (9-3,390 mU/ml). The diversity of serum EPO levels in patients with HIV infection and anemia suggests that the etiology of anemia in these patients and their potential response to recombinant human EPO may not be uniform.

Treating advanced ovarian cancer within the health maintenance organization: a Kaiser Permanente approach.

Treatment options for advanced ovarian cancer, a disease that is often terminal, are primarily palliative in nature and inherently expensive, presenting a dilemma for the managed care organization, whose purpose is to provide high-quality health care at a reasonable cost. Kaiser Permanente Northwest, a staff-model health maintenance organization providing care to patients in Oregon, Washington, and Idaho, has a unique approach to treating advanced ovarian cancer that involves the use of flexible evidence-based practice guidelines. These guidelines, which consist of state-of-the-art chemotherapy protocols, provide the Kaiser physician with the flexibility to treat each patient according to the particular stage and potential curability of the tumor. The Kaiser Permanente system controls costs by reducing hospital bureaucracy and encouraging treatment options that can be administered on an outpatient basis. Kaiser Permanente also makes use of multidisciplinary teams in the coordination of care and emphasizes the development of and participation in clinical research so that existing guidelines can be updated to reflect the best standards of cancer care.

Pulmonary Kaposi's sarcoma: clinical findings and results of therapy.

PURPOSE: Kaposi's sarcoma occurs commonly in patients with the acquired immunodeficiency syndrome (AIDS). Kaposi's sarcoma may remain localized or disseminate to involve visceral organs such as the lungs. Disseminated pulmonary involvement, when it occurs, is often fatal. Effective therapy may improve survival in such patients. We herein report on 20 patients with disseminated pulmonary Kaposi's sarcoma treated with cytotoxic chemotherapy. PATIENTS AND METHODS: Twenty previously untreated patients with pulmonary Kaposi's sarcoma were identified. All were treated with cytotoxic chemotherapy consisting of either Adriamycin alone, a combination of Adriamycin, bleomycin, and vincristine (ABV), or bleomycin and vincristine (BV). The response to therapy and factors affecting prognosis were analyzed retrospectively. RESULTS: Twelve (60%) patients showed a favorable response to therapy. The median survival from the initiation of chemotherapy for the 12 responders was 10 months (range: three to 31 + months) versus six months (range: one to 17+ months) for the non-responders. Eleven of the patients showing a response received ABV or BV combination chemotherapy (p = 0.004). Survival was shortened by the presence of either pleural effusion (p = 0.002), T4 lymphopenia of less than 100/mm3 (p = 0.03), or both at study entry. CONCLUSIONS: In patients with pulmonary Kaposi's sarcoma, combination chemotherapy consisting of ABV or BV is associated with dramatic clinical and functional improvement. The median survival of 10 months demonstrates the value of combination chemotherapy in this group of patients.

Systemic treatment of AIDS-related Kaposi's sarcoma: results of a randomized trial.

PURPOSE: Patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma generally respond well to cytotoxic chemotherapy. However, due to the associated myelosuppression, these patients are at risk for developing complicating infections that may affect survival. We therefore conducted a multi-center randomized clinical trial comparing single-agent against combination chemotherapy in advanced AIDS-related Kaposi's sarcoma. Low-dose chemotherapy was employed to evaluate its role in combination therapy for this disease and the toxicities associated with the lower intensity. PATIENTS AND METHODS: Sixty-one patients with extensive mucocutaneous Kaposi's sarcoma or visceral involvement were randomized for treatment with low-dose Adriamycin (doxorubicin, 20 mg/m2) alone (31 cases) or in combination with bleomycin and vincristine (ABV) (30 cases). Patients were randomized within strata based on prognostic features associated with shorter survival in prior studies. Both treatment arms were evenly matched at study entry. RESULTS: Complete and partial tumor remissions were significantly higher with ABV (88%) than with Adriamycin alone (48%) (p = 0.004). The median survival was 9 months in both groups. Study entry criteria significantly associated with shorter survival included CD4 lymphocyte counts less than 100/mm3, hemoglobin level less than 10 g/dL, a history of constitutional symptoms, and a prior history of opportunistic infection(s). Toxicities were similar in both arms, and the regimens were well tolerated. Neutropenia (granulocyte count less than 1,000/mm3) occurred in 34% of patients receiving Adriamycin alone and in 52% of patients receiving ABV and was progressive in successive courses of chemotherapy in both treatment arms. The development of AIDS-defined opportunistic infections was relatively infrequent during therapy (14%). CONCLUSIONS: Low-dose ABV is an effective chemotherapy regimen for the treatment of extensive Kaposi's sarcoma. ABV chemotherapy is associated with significantly higher responses than Adriamycin alone and with acceptable toxicity.

Treatment of advanced Kaposi's sarcoma using a combination of bleomycin and vincristine.

Eighteen patients with disseminated AIDS-related Kaposi's sarcoma (KS) and compromised bone marrow function were treated with a relatively non-myelosuppressive regimen of bleomycin and vincristine (BV). At study entry, the patients presented with the following median laboratory values: hemoglobin of 9.5 g/dl, granulocyte counts of 1,173/mm3, platelet counts of 218,000/mm3, and CD4 lymphocyte counts of 58/mm3. All patients had extensive Kaposi's sarcoma. Nine patients had visceral involvement: four with pulmonary involvement, two with gastrointestinal involvement, and three with both. Following a median number of seven cycles of biweekly chemotherapy, complete or partial tumor responses were achieved in 13 patients (72%). Two patients experienced bleomycin-induced skin toxicities, whereas 10 others (55%) experienced peripheral sensory neuropathy requiring vincristine dose reductions. Opportunistic infections had occurred in 11 patients prior to initiation of chemotherapy and in 16 after initiation of chemotherapy. Despite the frequent development of opportunistic infections, BV chemotherapy was relatively well tolerated and resulted in a high response rate in this patient population that presented with suboptimal marrow function and extremely low CD4 lymphocyte counts.