In addition to proliferating cancer cells and various types of normal cells, such as those of the bone marrow, conventional cytotoxic chemotherapeutics affect the endothelium of the growing tumour vasculature. The anti-angiogenic efficacy of chemotherapy seems to be optimized by administering comparatively low doses of drug on a frequent or continuous schedule, with no extended interruptions — sometimes referred to as 'metronomic' chemotherapy. In addition to reduced acute toxicity, the efficacy of metronomic chemotherapy seems to increase when administered in combination with specific anti-angiogenic drugs. Gaining better insight into the mechanisms of these effects could lessen or even eliminate the empiricism used to determine the optimal dose and schedule for metronomic chemotherapy regimens.

/pdf/the-anti-angiogenic-basis-of-metronomic-chemotherapy-41lcl013si.pdf

The anti-angiogenic basis of metronomic chemotherapy

Purpose The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. Patients and Methods Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m2 on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. Results The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naive patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic dea...

Phase II Trial of Weekly Paclitaxel for Unresectable Angiosarcoma: The ANGIOTAX Study

Kaposi sarcoma (KS) remains a challenge. Its classic or Mediterranean form tends to be benign. In transplant recipients it may be less so. As part of the AIDS pandemic, of which it was an original defining component, it may be life-threatening. It is due to human herpesvirus-8, which is necessary but not sufficient to produce the disease. KS has a low prevalence in the general population of the United States and United Kingdom, with an intermediate rate in Italy and Greece, and a high one in parts of Africa. In Italy, hot spots include its southern regions, the Po River Valley, and Sardinia, possibly related to a high density of blood-sucking insects. An important challenge is to treat KS patients without immunocompromising them. The potential of effective anti-herpes virus therapy and the use of sirolimus in transplantation recipients have added new opportunities for KS prevention. Learning objectives At the conclusion of this learning activity, participants should be able to provide the most recent information about Kaposi sarcoma in the context in which it occurs. Its classic or Mediterranean form, its pattern in transplant recipients and others iatrogenically immunosuppressed, and its occurrence as a potentially life-threatening part of the AIDS pandemic will be stressed. Its etiology and transmission will be discussed in detail to facilitate understanding of Kaposi sarcoma and of human herpesvirus-8 infection in the general population of the United States and United Kingdom, in Italy and Greece, and in certain parts of Africa. Its therapy, including the concept of doing it without immunocompromising the patient, will be stressed. New opportunities for Kaposi sarcoma prevention will also be discussed.

Kaposi sarcoma: a continuing conundrum.

M Bower, S Collins, C Cottrill, K Cwynarski, S Montoto, M Nelson, N Nwokolo, T Powles, J Stebbing, N Wales and A Webb, on behalf of the AIDS Malignancy Subcommittee Department of Oncology, Chelsea & Westminster Hospital, London, UK, HIV i-Base and UK-CAB, London, UK, St Bartholomew’s Hospital, London, UK, Royal Free Hospital, London, UK, Hammersmith Hospital, London, UK and Royal Sussex County Hospital, Brighton, UK

https://onlinelibrary.wiley.com/doi/pdf/10.1111/hiv.12136

British HIV Association guidelines for HIV-associated malignancies 2014

This paper discusses the importance of oral lesions as indicators of infection with human immunodeficiency virus (HIV) and as predictors of progression of HIV disease to acquired immunodeficiency syndrome (AIDS). Oral manifestations are among the earliest and most important indicators of infection with HIV. Seven cardinal lesions, oral candidiasis, hairy leukoplakia, Kaposi sarcoma, linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis and non-Hodgkin lymphoma, which are strongly associated with HIV infection, have been identified and internationally calibrated, and are seen in both developed and developing countries. They may provide a strong indication of HIV infection and be present in the majority of HIV-infected people. Antiretroviral therapy may affect the prevalence of HIV-related lesions. The presence of oral lesions can have a significant impact on health-related quality of life. Oral health is strongly associated with physical and mental health and there are significant increases in oral health needs in people with HIV infection, especially in children, and in adults particularly in relation to periodontal diseases. International collaboration is needed to ensure that oral aspects of HIV disease are taken into account in medical programmes and to integrate oral health care with the general care of the patient. It is important that all health care workers receive education and training on the relevance of oral health needs and the use of oral lesions as surrogate markers in HIV infection.

/pdf/oral-lesions-in-infection-with-human-immunodeficiency-virus-21kbbbtz4c.pdf

Oral lesions in infection with human immunodeficiency virus

BACKGROUND

Treatment options are limited for patients with advanced acquired immunodeficieny syndrome (AIDS)-related Kaposi sarcoma (AIDS-KS) whose disease has progressed after receiving therapy with liposomal anthracyclines or combination chemotherapy with doxorubicin (Adriamycin), bleomycin, and vincristine (ABV). This study was performed to assess the safety and efficacy of a novel dose and schedule of paclitaxel in patients with AIDS-KS who failed to respond to previous systemic chemotherapy.



METHODS

This was an open-label, multicenter Phase II study. Eligible patients had advanced AIDS-KS consisting of at least 25 mucocutaneous lesions, visceral disease, or lymphedema, and had failed to respond to at least one previous systemic chemotherapy regimen. Patients were treated with paclitaxel at a dose of 100 mg/m2 given intravenously over 3 hours, every 2 weeks. Primary efficacy end points were tumor response, time to progression, time to treatment failure, and survival. Quality of life and adverse events were evaluated using the Symptom Distress Scale (SDS) and the World Health Organization Toxicity Criteria, respectively.



RESULTS

One hundred and seven male patients with advanced AIDS-KS were enrolled from nine participating sites. The median entry CD4+ lymphocyte count was 41/mm3 (range 0–1139). Previous treatment regimens included ABV in 52, liposomal daunorubicin in 49, and liposomal doxorubicin in 40 patients. Forty-one patients (38%) received two or more previous chemotherapy regimens. Protease inhibitor use during the study was reported by 82 (77%) patients overall; 47 patients (44%) were receiving a protease inhibitor before study entry. Complete or partial response was documented in 60 patients (56%). The median duration of response was 8.9 months. Major response rate was similar when comparing patients not on a protease inhibitor at the time of response (59%) with patients on a protease inhibitor at time of response (54%). However, protease inhibitor use had a significant impact on survival (P = 0.04). Grade 4 neutropenia was reported in 35% of patients; other life-threatening side effects were uncommon. Significant improvements were seen in the total quality of life scores measured by the SDS, including significant improvement in KS-related symptoms such as facial disease, tumor-associated edema, and pulmonary involvement.



CONCLUSION

Paclitaxel given every 2 weeks induces major tumor regression in the majority of patients with advanced KS who failed to respond to previous systemic chemotherapy. Paclitaxel is associated with significant improvement in quality of life with acceptable toxicity and should be considered as an effective treatment option for patients with advanced KS. Cancer 2002;95:147–54. © 2002 American Cancer Society.



DOI 10.1002/cncr.10634

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.10634

Jerome Groopman

Papers

Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma.