ABSTRACT
To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg(-1), mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg(-1), clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg(-1) when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (> or =280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy.
Subject(s)
Angiogenesis Inhibitors/toxicity , Neoplasms/drug therapy , Oligopeptides/toxicity , Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Oligopeptides/administration & dosage , Oligopeptides/pharmacokineticsSubject(s)
Sarcoma, Kaposi/therapy , Skin Neoplasms/therapy , Anthracyclines/administration & dosage , Anthracyclines/therapeutic use , Antineoplastic Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Antiviral Agents/therapeutic use , CD4 Lymphocyte Count , Clinical Trials as Topic , Cryotherapy , Drug Therapy, Combination , HIV Infections/complications , HIV-1 , Herpesvirus 8, Human , Humans , Interferons/therapeutic use , Liposomes , Physical Examination , Practice Guidelines as Topic , Prognosis , Respiratory Tract Neoplasms/pathology , Retinoids/administration & dosage , Retinoids/therapeutic use , Sarcoma, Kaposi/complications , Sarcoma, Kaposi/pathology , Skin Neoplasms/complications , Skin Neoplasms/pathology , Viral LoadABSTRACT
Breast cancer is the most common malignancy among American women. As a result of widespread screening, most patients present with operable breast cancer that is treated with curative intent. It is well established that the appropriate use of adjuvant therapy improves the disease-free and overall survival of patients with breast cancer. Adjuvant systemic therapy options include tamoxifen for hormone receptor-positive patients, and systemic polychemotherapy. It is standard clinical practice to administer adjuvant systemic therapy to patients with node-positive and high-risk, node-negative breast cancer.
Subject(s)
Breast Neoplasms/surgery , Neoplasms, Hormone-Dependent/surgery , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/radiotherapy , Cisplatin/administration & dosage , Combined Modality Therapy , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Methotrexate/administration & dosage , Neoadjuvant Therapy , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Hormone-Dependent/mortality , Neoplasms, Hormone-Dependent/radiotherapy , Practice Guidelines as Topic , Survival Analysis , Tamoxifen/therapeutic useABSTRACT
Kaposi's sarcoma (KS) is the most common malignancy associated with human immunodeficiency virus-1 (HIV-1) infection and can result in significant morbidity. The clinical course of KS is quite variable, although for the majority of patients, KS is ultimately a progressive disease requiring systemic therapy. For early indolent KS, local therapies may be appropriate and may provide significant palliation. For patients with more advanced or rapidly progressive disease, systemic therapy is the treatment of choice. Interferon-alfa (Intron A, Roferon-A), with or without antiretroviral agents, is particularly useful for patients with relatively preserved immune function. For patients with symptomatic visceral disease, pulmonary disease, or rapidly progressive cutaneous disease, chemotherapy is the treatment of choice. An increasing number of agents are now available for the treatment of KS. Pathogenesis-based treatment and/or preventive therapies based on the recognized association between KS-associated herpesvirus (KSHV) and KS are likely to be available in the near future.
