The results of a Phase I extension study, presented at the 15th Congress of the European Cancer Organisation and the 34th Congress of the European Society for Medical Oncology joint conference in Berlin, Germany, suggest a significant advance in the treatment of metastatic melanoma.
Advanced melanoma represents one of the most difficult cancers to treat successfully once it has become metastatic, rapidly spreading to almost anywhere in the body, notably to the lymph nodes, lungs, liver and brain, whereby the prognosis becomes dismal.
In this study, 31 melanoma patients carrying the cancer-causing BRAF mutation were treated with 960 mg of PLX4032 twice daily. A total of 14 out of 22 evaluable patients met the official criteria for partial response of tumor shrinkage of at least 30% for at 1 month, while six more also showed a response; however, at the time of the congress presentation, it was too early to say whether the tumors would shrink far enough to meet these criteria.
Paul Chapman of the Memorial Sloan–Kettering Cancer Center (NY, USA), one of the leaders of the trial, exclaimed “We are very excited about these results. Of the 22 patients we have been able to evaluate so far, 20 have had some objective tumor shrinkage. This is impressive as they all had metastatic disease and most of them had failed several prior therapies.”
“We are seeing some pretty dramatic and rapid responses, and they are occurring in sites where we rarely see responses to chemotherapy, such as in the bone. We don’t know yet how long these responses will last, and we have had patients whose cancer has progressed after initially responding; so we are putting a lot of effort in to studying the patients who do relapse, trying to understand how their tumors have become resistant”, he continued.
Phase II and III trials are planned to begin later this year or early next year.
While Chapman conceded that it was too early to be talking about a cure for advanced melanoma, he feels the drug has great potential. “Most of us think that a drug like this would ultimately be part of the regimen, but that we might need additional drugs with it to complete the cure. Right now we are seeing dramatic responses, but it’s too early to say whether we’ve actually cured people because most patients still have evidence of some level of tumor on their skin. I think this is a huge step forward; whether or not it will be sufficient by itself really remains to be seen.”
Source: ECCO–ESMO joint conference press release: Trial of new treatment for advanced melanoma shows rapid shrinking of tumors www.ecco-org.eu/Conferences-and-Events/ECCO-15-ESMO-34/Press-Release/List-of-press-releases/Trials-of-two-treatments-for-advanced-melanoma-sho/page.aspx/1836
The incidence of certain cancers, including anal, lung and melanoma, is significantly increased in HIV-infected persons in a large cohort of veterans regardless of age.
A research team at UT Southwestern Medical Center (TX, USA) scrutinized the medical records of more than 100,000 patients in the US Veteran Affairs Healthcare system for rates of cancer between 1997 and 2004, and adjusted the statistics for age, ethnicity and gender.
HIV-infected patients were 60% more likely to have Hodgkin’s lymphoma, melanoma, lung, liver or anal cancer, although rates of prostate cancer were similar between the 33,420 HIV-infected and 66,840 non-infected patients in which men predominate.
There is a well-established link between HIV infection and specific opportunistic cancers, such as non-Hodgkin’s lymphoma, Kaposi’s sarcoma and cervical carcinoma. As life expectancy increased with the advent of antiretroviral therapy, cases of other cancers increased in the HIV-infected population.
“It’s a genuine increase in the incidence of these cancers,” said Roger Dedimo, lead author of the study published in the Journal of Acquired Immune Deficiency Syndromes. “The increase is more visible because these patients are living longer, but our findings suggest that the increased number of non-AIDS-defining malignancies is not simply the result of their longer lives,” considers Dedimo.
The incidence-rate ratio of HIV-infected to HIV uninfected was 1.6 (1260 versus 841 per 100,000 person-years). Anal cancer ranked most common proportionally and among the HIV-infected group, and those diagnosed with cancer had a lower CD4+ count of 249 versus 270 (p = 0.03).
The underlying reasons for why HIV infection is associated with these types of cancer remains unclear. The role of viral infection, the effects of treatment and the lifestyle choices of HIV-infected persons require further investigation. The team will next analyze other immune function in patients with and without cancer.
“We also know that HIV does a lot more to your immune system than just decrease the number of these cells,” says Bedimor, “it’s very possible that it is an immune dysfunction that impairs the cancer immune surveillance in patients even after their CD4 counts have increased.”
Sources: Bedimo RJ, McGinnis KA, Dunlap M et al.: Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression. J. Acquir. Immune Defic. Syndr. [Epub ahead of print] (2009); www.utsouthwestern.edu/home/news/index.html
New research led by James Lawson at the University of New South Wales (UNSW) School of Biotechnology and Biomolecular Sciences (NSW, Australia) claims to have ‘unambiguously’ demonstrated the presence of high-risk human papillomavirus (HPC) in the nuclei of breast cancer epithelial cells, leading to the proposal that HPV, as an oncogenic hormone-dependent virus, plays a role in not only cervical and head and neck cancers, but also a causal role in human breast cancer.
This hypothesis has been considered controversial due to the widely varying results that report the prevalence of HPV-positive breast cancer range from 4 to 86%. The difficulty in detecting the virus in breast specimens and the risk of contamination during PCR has led to distrust and criticism of previous findings.
By using in situ PCR and thus avoiding cross-contamination, the group at UNSW believes that they have overcome this problem, meaning that the low levels of HPV detected in their study are not artifacts. The group acknowledge the presence of HPV in some normal breast tissue, and therefore suggest only a causal relationship to breast cancer. However, the team propose that this role of HPV could mean that vaccination against HPV may act as a primary prevention against breast cancer.
Source: Heng B, Glenn WK, Ye Y et al. Human papilloma virus is associated with breast cancer. Br. J. Cancer (2009) (Epub ahead of print).
The US FDA has cleared a test that can help detect ovarian cancer in women already marked for surgery owing to a pelvic mass. The test, called OVA1, helps patients and healthcare professionals decide on an appropriate course of surgical treatment; it is recommended for use by primary care physicians and gynecologists as an adjunctive test to complement, but not replace, other diagnostic and clinical procedures.
Developed by Vermillion Inc., CA USA, in conjuction with researchers at The Johns Hopkins University, MD, USA, OVA1 tests a blood sample for levels of five proteins that are known to alter in cases of ovarian cancer. The five separate results for each protein are converted into a single numerical score between 0 and 10, and this score can be used to indicate the likelihood of the pelvic mass being malignant.
The US FDA reviewed a study of 516 patients that compared OVA1 results with biopsy results. When combined with other presurgical test results, such as radiography tests, results from the OVA1 tests identified additional pelvic mass patients who might benefit from oncology referral, who were not identified using presurgical information alone.
The OVA1 test is designed for use in women aged 18 years or older, and identifies some women who will benefit from referral to a gynecological oncologist for their surgery, despite previously receiving negative results from other tests for ovarian cancer. If other test results suggest malignancy, referral to an oncologist is appropriate even if the OVA1 test shows a negative result, as the test is not intended to ovarian cancer screening or for a definitive diagnosis of ovarian cancer.
Previously published guidelines by The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists regarding the role of generalist obstetrician–gynecologists in the early detection of ovarian cancer recommended referral of a patient to a gynecological oncologist when specific indicators of malignancy are present. These recommendations and subsequent reports indicate that patients with ovarian cancer have improved survival when the surgery is performed by gynecologic oncologists as opposed to general gynecologists or surgeons.
“Tests such as OVA1 personalize and improve public health by providing patients and healthcare providers with more information to support medical decisions that impact survival rates and reduce surgical complications,” claims Jeffrey Shuren, Acting Director of the US FDA’s Center for Devices and Radiological Health.
Source: www.fda.gov