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PURPOSE, Patients with acuuired 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 We therefore conducted a multicenter, randomized clinical trial comparing single-agent against combination chemotherapy in advanced AIDS-relaed Kaposi's sarcoma. Lowdose chemotherapy was employed to evaluate its role in combination therapy for this disease and the toxicities assocated with the lower intensity. PATIENTS AND METHODS: Sixty-one patients with extensive mucocutaneous Karposi's sarcoma or visceral involvement were randomized for treatment with low-dose Adriamycin (doxorubicin, 20 Mg/Mm.sup.2) alone (31 cases) or in combination with bleomycin and vincristine (ABV) (30 cases). Patients were randomized within strata based on prognostice 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/mm.sup. 3, 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/ mm.sup.3) occurred in 34% of patients receiving Adriamycin alone and in 52% of patients receiving ABV and was propressive 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., Kaposi's sarcoma (KS) is a rare form of cancer, characterized by skin tumors, that is often seen in patients with acquired immunodeficiency syndrome (AIDS). The cancer often spreads throughout the body if the patient does not die of other infections first and if treatment is not given. A number of chemotherapy treatments have been tested in treating KS in AIDS patients. Varying results have been obtained and a number of side effects, including further immune suppression, have developed. Low doses of the drug Adriamycin (doxorubicin) have been effective in fighting KS with minimal effects upon bone marrow function. This study compared a regimen of alternating low doses of this drug and low doses of bleomycin and vincristine (ABV) with doxorubicin alone for treating KS. Sixty-one KS patients infected with human immunodeficiency virus (HIV) were assigned to treatment with either ABV or doxorubicin alone, every two weeks. Eight of the subjects had to be withdrawn from the study because of other complications. In the 53 remaining patients, 88 percent of those receiving ABV had positive responses, while only 48 percent receiving doxorubicin alone did. Complete remission was attained in 38 percent of the patients receiving ABV but only 3 percent of those receiving doxorubicin alone. At long-term follow-up, 72 percent of the patients had died, mainly from infectious diseases. A number of treatment-related side effects, generally acceptable ones, occurred in both groups and the incidence of infectious disease was relatively low and similar in both groups during treatment. Bone marrow suppression was generally minimal, although levels of granulocytes (a type of white blood cell) did decrease in a number of patients. These results indicate that ABV therapy can be effective in treating KS without major side effects. Use of granulocyte stimulating-factors in conjunction with this treatment may help prevent the side effects that were seen. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kaposi's sarcoma is common among patients with AIDS, and is present at the initial diagnosis of AIDS in almost 10 percent of the cases. Although the tumor can be controlled by chemotherapy, the use of effective doses is prohibited by the depressed state of the immune system in these patients. The bone marrow suppression resulting from chemotherapy combined with the preexisting immune deficiency usually leaves the patient vulnerable to opportunistic infections. Indeed, most patients treated for Kaposi's sarcoma die of infection with Pneumocystis carinii, which causes pneumonia. In order to determine if a more conservative regimen of chemotherapy might prove to be effective against Kaposi's sarcoma, 33 patients were treated with a combination of doxorubicin, bleomycin, and vincristine. Two different dosages of doxorubicin were evaluated. Eight patients achieved complete responses and 18 achieved partial responses, for a total response rate of 79 percent. While the drug combination proved to be efficacious, opportunistic infections were common among the patients. A total of 23 patients developed opportunistic infections, 17 with Pneumocystis carinii. In addition, the duration of the response itself was short, with all patients relapsing by twelve weeks from the end of treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Pneumocystis carinii (Pc) pneumonia occurs in more than 80 percent of AIDS cases, and is one of the primary causes of death in patients with AIDS. The current therapy for Pc pneumonia consists of trimethoprim-sulfamethoxazole (T-S) or pentamidine isethionate (P-I), and produces significantly adverse side effects in as many as 80 percent of patients. Nonetheless, Pc pneumonia mortality ranges between 40 and 60 percent of cases. Trimetrexate (TX) is a new agent with promising effects. Its mode of action is the same as T-S, but it is 1,500 times more effective in binding to dihydrofolate reductase of pneumocystis. The addition of leucovorin (5-formyl tetrahydrofolate; LV) protects the patient's cells from the cytotoxic effects of TX. Used together, TX-LV should be a significant adjunct to the current formulary of AIDS patients with Pc pneumonia. A group of 54 AIDS patients with Pc pneumonia were enrolled in a dosage evaluation trial with TX-LV. Varying dosage schedules and combinations were administered, and the side effects, particularly hematologic (blood-related) in nature, were assessed. A full treatment course consisted of 21 full doses of TX. Therapeutically effective combination doses were achieved at 45 milligrams per square meter per day of TX and 80 milligrams per square meter per day of LV. Further control studies are recommended to compare the safety and effectiveness of these drugs with other medications used to treat Pc pneumonia. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects habouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG.Methods VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including =1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8.Results The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was -1.06 log10copies/ml for the DTG arm and 0.10 log10copies/ml for the placebo arm (treatment difference -1.16 log10copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study.Conclusions The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.

Todetermine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levelsof neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%),9 (75%), and 4 (67%) patients in the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%),10 (100%),7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m-zday dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.