Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team.

1998 ◽  
Vol 16 (4) ◽  
pp. 1444-1449 ◽  
Author(s):  
B J Dezube ◽  
J H Von Roenn ◽  
J Holden-Wiltse ◽  
T W Cheung ◽  
S C Remick ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Partial Response ◽  
Kaposi's Sarcoma ◽  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Kaposi’S Sarcoma ◽  
Trial Group ◽  
Cutaneous Lesions ◽  
Aids Clinical Trial Group ◽  
Dose Levels

PURPOSE Angiogenesis is a major component of Kaposi's sarcoma (KS) and a critical process in tumor growth. The present study was designed primarily to test the toxicity and pharmacokinetics (PK) of the angiogenesis inhibitor TNP-470 and secondarily to evaluate tumor response in patients with early AIDS-related KS. PATIENTS AND METHODS Patients with AIDS-related KS were required to have cutaneous disease with > or = 5 measurable lesions and no evidence of pulmonary, symptomatic gastrointestinal, or acutely life-threatening KS. Thirty-eight patients received TNP-470 by weekly intravenous infusion over 1 hour at one of six dose levels for up to 24 weeks. RESULTS The dose levels tested included 10, 20, 30, 40, 50 and 70 mg/m2. Median CD4 count was 24 cells/microl (range, 0 to 460). Fourteen patients (36%) had > or = 50 cutaneous lesions and 19 (49%) had oral lesions. Adverse events included neutropenia (n = 2), hemorrhage (n = 3), and urticaria (n = 1). PK studies showed wide interpatient and intrapatient variability. Elimination half-life values were short (range, 0.01 to 0.61 hours). Seven patients (18%) achieved a partial response. The median time to partial response was 4 weeks (range, 2 to 25), and the median duration of response was 11 weeks (range, 3 to 26+). CONCLUSION TNP-470, administered as a weekly, 1-hour infusion to patients with early AIDS-KS is well-tolerated at doses up to and including the highest dose tested. Tumor responses were observed in a substantial number of cases and occurred at various dose levels. TNP-470 should be evaluated further in patients with AIDS-KS as a single agent and in combination with other biologic response modifiers in early disease or after initial response to cytotoxic chemotherapy.

scholarly journals Transplant-associated penile Kaposi sarcoma managed with single agent paclitaxel chemotherapy: a case report

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Matthew A. Anderson ◽  
Tracey Ying ◽  
Kate Wyburn ◽  
Peter M. Ferguson ◽  
Madeleine C. Strach ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Single Agent ◽  
Lower Extremities ◽  
Kaposi’S Sarcoma ◽  
The Body ◽  
Cutaneous Lesions ◽  
Rare Presentation ◽  
Post Transplant ◽  
Transplant Patients ◽  
Disseminated Disease

Abstract Background Kaposi’s sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower extremities. Penile involvement has been reported only rarely. Management of cutaneous-limited disease is primarily reduction of immunosuppression and conversion to an mTOR-inhibitor, whereas the treatment of disseminated disease in transplant patients is more variable. Case presentation A 75-year-old male, originally from Somalia, received a deceased-donor kidney transplant for diabetic and hypertensive nephropathy. Seven months post-transplant he presented with lower limb lesions, oedema and bilateral deep vein thromboses. He then developed a fast-growing painful lesion on his penile shaft. A biopsy of this lesion confirmed KS, and a PET scan demonstrated disseminated disease in the lower extremities, penis and thoracic lymph nodes. His tacrolimus was converted to sirolimus, and his other immunosuppression was reduced. He was treated with single agent paclitaxel chemotherapy in view of his rapidly progressing, widespread disease. The penile lesion completely resolved, and the lower extremity lesions regressed significantly. His kidney allograft function remained stable throughout treatment. Conclusion This case illustrates a rare presentation of an uncommon post-transplant complication and highlights the need for a high index of suspicion of KS in transplant patients presenting with atypical cutaneous lesions. It serves to demonstrate that the use of single agent paclitaxel chemotherapy, switch to an mTORi and reduction in immunosuppression where possible produces excellent short-term outcomes, adding to the body of evidence for this management strategy in disseminated Kaposi’s sarcoma.

Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma.

1998 ◽  
Vol 16 (3) ◽  
pp. 1112-1121 ◽  
Author(s):  
L Welles ◽  
M W Saville ◽  
J Lietzau ◽  
J M Pluda ◽  
K M Wyvill ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Kaposi's Sarcoma ◽  
Single Agent ◽  
Kaposi’S Sarcoma ◽  
Complete Response ◽  
Pulmonary Involvement ◽  
Dose Titration ◽  
Treatment Schedule ◽  
Creatinine Concentration ◽  
Immunodeficiency Virus

PURPOSE To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. RESULTS Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. CONCLUSION Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease.

Paclitaxel Is Safe and Effective in the Treatment of Advanced AIDS-Related Kaposi's Sarcoma

1999 ◽  
Vol 17 (6) ◽  
pp. 1876-1876 ◽  
Author(s):  
Parkash S. Gill ◽  
Anil Tulpule ◽  
Byron M. Espina ◽  
Suzanne Cabriales ◽  
Jocelyn Bresnahan ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Median Duration ◽  
Systemic Therapy ◽  
Kaposi's Sarcoma ◽  
Single Agent ◽  
Kaposi’S Sarcoma ◽  
Duration Of Response ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

PURPOSE: Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. MATERIALS AND METHODS: A regimen of paclitaxel at a dose of 100 mg/m2 was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. RESULTS: Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4+ lymphocyte count was 20 cells/mm3 (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. CONCLUSION: Paclitaxel at 100 mg/m2 given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.

scholarly journals Rapid Progression of Kaposi’s sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection: a case report

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Pingzheng Mo ◽  
Liping Deng ◽  
Xiaoping Chen ◽  
Yong Xiong ◽  
Yongxi Zhang
Keyword(s):  
Hiv Infection ◽  
Kaposi's Sarcoma ◽  
Hemophagocytic Syndrome ◽  
Kaposi’S Sarcoma ◽  
Rapid Progression ◽  
Immunosuppressed Patient ◽  
Timely Manner ◽  
Cutaneous Lesions ◽  
Case Presentation ◽  
Life Threatening

Abstract Background AIDS-related KS generally involves cutaneous lesions, that slowly progress over months to years. Neither rapidly progressing of KS nor KS complicated with hemophagocytic syndrome (HPS) has rarely been reported. Case presentation We report a rare case of rapid progression of Kaposi’s sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection. The symptoms of this patient were atypical, showing only persistent high fever and rapid progressed to hemophagocytic syndrome. This patient was successfully treated with antiretroviral therapy combined with liposomal doxorubicin. Conclusions The condition of the KS patient could deteriorate rapidly over a period of days and even developeded into HPS, which was life-threatening. However, chemotherapy initiated in a timely manner might improve prognosis.

Safety and pharmacokinetics of intravenous VEGF Trap plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in a combination phase I clinical trial of patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13161-13161 ◽  
Author(s):  
O. Rixe ◽  
C. Verslype ◽  
J. B. Méric ◽  
S. Tejpar ◽  
J. Bloch ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Maximum Tolerated Dose ◽  
Vegf Receptor ◽  
Advanced Solid Tumors ◽  
Colon Cancers ◽  
Ecog Ps ◽  
Dose Levels ◽  
Vegf Trap

13161 Background: VEGF Trap is a potent angiogenesis inhibitor comprising portions of human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (Flk-1) extracellular domains fused to the Fc portion of human IgG. VEGF Trap binds VEGF and neutralizes all VEGF-A isoforms plus placental growth factor. I-LV5FU2 is an approved chemotherapy regimen for the first-line treatment of metastatic colorectal cancer. This study was designed to evaluate the safety and pharmacokinetics (PK) of VEGF Trap plus I-LV5FU2 administered intravenously. Methods: Successive cohorts of 3–6 patients (pts) with relapsed or refractory solid tumors received intravenous VEGF Trap plus I-LV5FU2 every 2 weeks. Study endpoints included safety, PK, and immunogenicity. Antitumor activity was assessed by CT scan. Results: Ten pts (3 male/7 female), median age 59 (34–67), ECOG PS 0/1/2: 8/2/0, with a variety of advanced solid tumors, including 5 colorectal and 2 ovarian, have received a total of 50 cycles of VEGF Trap plus I-LV5FU2 across 2 VEGF Trap dose levels (2.0 mg/kg, 4.0 mg/kg) to date. Only 1 dose-limiting toxicity (G3 proteinuria >2 wks with normal plasma creatinine levels) has been encountered so far (4.0 mg/kg, Cycle 2). This pt also had controlled G2 HTN (renal biopsy pending). No other G3/4 VEGF Trap-related AEs have been reported so far. Preliminary free VEGF Trap clearance was 15.4 mL/kg/day. Three pts (synovial sarcoma, ovarian and colon cancers) achieved partial responses. Conclusions: VEGF Trap may be safely combined with I-LV5FU2 at the dose levels studied. Preliminary free VEGF Trap clearance did not differ significantly from that seen with single-agent exposure; chemotherapy PK analysis is pending. The maximum tolerated dose has not yet been reached, and dose escalation continues. Updated safety, pharmacokinetic, and preliminary efficacy results from this ongoing study will be presented. [Table: see text]

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