Some early-stage prostate cancers benefit from hormonal therapy

BY ELIZABETH WHITTINGTON | MARCH 10, 2010

At the Genitourinary Cancers Symposium, held March 5-7 in San Francisco, researchers presented a study that showed men with early-stage prostate cancer can benefit from a combination of hormonal therapy and radiation therapy.

Knowing that not all men are at the same risk for recurrence, investigators of the phase 3 RTOG 94-08 study analyzed the results after stratifying nearly 2,000 men as being low-, intermediate-, or high-risk for recurrence. They found that men with intermediate risk who received short-term total androgen suppression and radiation lived longer than men with similar risk who received radiation only. Intermediate risk was defined as having a Gleason score of 7, or a score of 6 or less with either a PSA between 10 and 20 or a staging subcategory of T2b (where cancer is present in 50 percent of one lobe of the prostate gland).

Intermediate-risk patients in the combination arm received a total of four months of hormonal therapy, with radiation therapy beginning after two months. After two years, a repeat biopsy was performed in 843 men to gauge recurrence--of 439 men who received the combination therapy, 78 percent had no sign of a recurrence; in the 404 men who received just radiation, only 60 percent had no evidence of cancer. After 12 years of follow-up, 51 percent of intermediate-risk patients in the combination group were alive compared with 46 percent in the radiation-alone group. Researchers noted that previous studies show that men at high-risk should receive more than four months of hormonal therapy, so there was more focus on the results for intermediate-risk patients.

Researchers also found that men with low-risk disease did not benefit from the combination, which highlights another interesting point about the new way we're studying medicine. If all of the patients receiving the combination had been lumped into just one group, the results would have not been as dramatic. It might also have driven some men to undergo the cost, side effects, and inconvenience of a therapy that would ultimately have had no benefit for them. Continuing to analyze subgroups in trials such as these will show us how best to use certain therapies for certain patients.

The benefit of the combination in intermediate-risk patients could be even greater than what the study initially suggests. While researchers designed the study using radiation therapy that was standard in 1994, the field has seen many advances since then, such as being able to provide higher, more targeted--and albeit, safer--doses. A new trial called RTOG 0815 will be studying men with intermediate-risk, early-stage prostate cancer, but using 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy with androgen deprivation therapy to see if the benefit of the combination still exists. (You can read more about these radiation techniques in "Targeted Strike.") Details of the RTOG 0815 clinical trial can be found at clinicaltrials.gov.

New drug extends survival in advanced chemo-resistant prostate cancer

BY ELIZABETH WHITTINGTON | MARCH 5, 2010

Results announced at the Genitourinary Cancers Symposium this week show impressive gains in prostate cancer, especially those with metastatic cancer and few treatment options. For men with chemotherapy-resistant advanced prostate cancer, hope may be in a new investigational chemotherapy presented at the meeting being held today through Sunday in San Francisco.

Although most prostate cancers respond to hormonal therapy, or androgen deprivation therapy, some do not. These hormone-resistant prostate cancers are usually treated with Taxotere (docetaxel), but if patients progress on the drug, patients usually have few, if any, options. A newer generation taxane-based drug, cabazitaxel, could provide those patients with another treatment.

The drug was shown to increase median survival by 30 percent. Of the 755 patients in the study, those who received cabazitaxel lived a median of 15.1 months compared with about 12.7 months in patients taking mitoxantrone--a highly significant difference, said Oliver Sartor, MD, who presented the study.

Patients with this type of advanced prostate cancer usually have about a year survival, but Sartor noted that twice as many patients reached the two-year survival mark with cabazitaxel. "It is also, I think, particularly meaningful for patients who really don't have other alternatives today," Sartor said at a press briefing prior to the conference.

Nicholas Vogelzang, MD, who moderated the press briefing Wednesday, noted that although a three month survival advantage may seem small, it is a huge advancement in terms of cancer research. "Almost all the advances in [cancers] have come in these sorts of incremental advances. Three months is a major clinical advance," he told reporters. "It is exactly the same difference that led the FDA to approve docetaxel, and docetaxel now has become more and more widely used."

The phase III international study, called TROPIC, compared cabazitaxel, which is administered intravenously once every three weeks, with mitoxantrone, a commonly used chemotherapy, but one that has shown no survival benefit in this patient population. Sartor noted that researchers chose to use mitoxantrone to give patients an active therapy, as opposed to a placebo. All patients received the steroid prednisone. Further results of the study will be presented at the 2010 ASCO annual meeting in early June, including progression-free survival, tumor response rates, and prostate-specific antigen (PSA) response. However, researchers have suggested that those results are also favorable.

The maker of cabazitaxel, Sanofi-Aventis, is working with the FDA on submitting the drug for approval soon and was granted fast-track status in December. If approved, it could be available as early as end of this year.

Vogelzang said the argument could also be made now that the drug could be used earlier, "...now that there is something that works, the therapy might be given earlier and the survival advantage could potentially become even greater."

Current trials are looking into whether the drug should be given before hormone-resistant cancers progress on Taxotere, as well as in other tumor types.

You can view the study abstract at www.asco.org.

New breast cancer combination approved

BY ELIZABETH WHITTINGTON | FEBRUARY 2, 2010

Although Tykerb has already been approved for HER2-positive metastatic breast cancer, most patients must wait until they progress on other therapies before they are offered the targeted agent. But late Friday, the Food and Drug Administration granted Tykerb (lapatinib) accelerated approval as a first-line treatment in combination with Femara (letrozole).

The regimen is approved for postmenopausal women with ER-positive, HER2-positive metastatic breast cancer. It pairs Tykerb, which targets EGFR and HER2, with Femara, an aromatase inhibitor approved for ER-positive breast cancer.

The FDA based its approval on a study that included 219 women with ER-positive, HER2-positive cancer. Researchers found that Tykerb/Femara increased median progression-free survival by more than five months compared with Femara alone (8.2 months compared with 3 months). The most common side effects noted in the trial were diarrhea, rash, nausea, and fatigue.

For more information, read A Winning Combination, which covers the study presented at the 2008 San Antonio Breast Cancer Symposium. During the meeting, several researchers and oncologists noted the significance of the study results.

"This is huge improvement. This is very important information," said Edith Perez, MD, a professor of medicine at the Mayo Clinic and HER2-positive breast cancer researcher, during the 2008 meeting. There was also evidence that suggested the Tykerb and Femara combination could have the potential to benefit patients who relapsed on tamoxifen.

Tykerb was originally approved in 2007 in combination with Xeloda (capecitabine) for women with advanced or metastatic HER2-positive breast cancer, but only after they progressed on chemotherapy and Herceptin (trastuzumab). However, it is not known if the recently approved regimen is better than Herceptin (trastuzumab) in this patient population.

Season for rare lymphomas: new drug approved for CTCL

BY ELIZABETH WHITTINGTON | NOVEMBER 10, 2009

This must be the season for drug approvals for rare lymphomas--an early Christmas gift to many patients suffering from a rare blood cancer.

Folotyn (pralatrexate), which was approved in September for peripheral T-cell lymphoma came less than one month after an advisory committee recommended its approval. This time, it's patients with cutaneous T-cell lymphoma, a group of rare non-Hodgkin lymphomas that affect the skin, that are the recipients of a new treatment option.

CTCL is often mistaken at first for a rash and can cause itchy, red disfiguring patches. Current treatments for CTCL can include chemotherapy, radiation, or topical therapies. A new treatment, Istodax (romidepsin) was approved on November 5 for CTCL patients who have progressed on at least one prior therapy.

The Istodax approval was based on two studies that looked at a total of 167 CTCL patients who had either one or two prior therapies. The studies did not have a comparison arm. The overall response rate was about 34 percent with 6 percent of patients experiencing a complete response--a total remission from their cancer. The median length of response rate was 15 months (range of 1 to 20-plus months) in one study and 11 months (range of 1 to 66-plus months) in the second. Common side effects seen in the studies included nausea, fatigue, infection, and anemia.

Istodax is a histone deacetylase (HDAC) inhibitor, a class of drugs that works by helping the cell to package its DNA correctly around proteins called histones, by either unwinding genes that control cell growth or constricting those that invite unchecked cell division. You can read more about HDAC inhibitors, including other treatments in this drug class, in our feature on epigenetics, "Medicine's New Epicenter? Epigenetics" from our Winter 2008 issue.

FDA advisory panel unanimously recommends new kidney cancer drug

BY ELIZABETH WHITTINGTON | OCTOBER 6, 2009

Update [Oct. 20]: Pazopanib gets FDA approval. Read more...

There is probably no other cancer that has seen such breakthroughs in the past five years than kidney cancer. Less than a decade ago, patients with advanced renal cell carcinoma were treated with biological therapies, including interferon and interleukin, with few results. But in the past five years, there have been five drugs approved for the cancer--Sutent, Nexavar, Avastin, Torisel, and Afinitor.

Yesterday, the Oncologic Drugs Advisory Committee, a panel that reports to the Food and Drug Administration on whether a cancer drug should be approved or not, unanimously gave its recommendation for pazopanib. The panel said the drug appeared to be effective and its side effects were no more severe than other recently approved kidney cancer drugs.

The drug may also be a better alternative to some patients unable to tolerate the side effects of pazopanib's competitors. While studies show that pazopanib had a lower risk of rash and fatigue than with other kidney cancer drugs, some patients did develop diarrhea, hypertension, and nausea. The risk of severe liver injury, although rare, has also been noted.

Pazopanib, recently given a brand name of Votrient, was highlighted at this year's American Society of Clinical Oncology annual meeting where a phase III study compared the drug to placebo. Results showed the median progression-free survival in all patients more than doubled from 4.2 months with placebo to 9.2 months on pazopanib. (Newly diagnosed patients had improved PFS from 2.8 months to 11.1 months, while patients with prior biological treatment improved from 4.2 months to 7.4 months on the drug.)

Because there are so many kidney cancer drugs on the market now, some question whether pazopanib should be approved based on a placebo study. A phase III trial looking at the drug versus Sutent--the standard treatment for advanced kidney cancer--in locally advanced or metastatic RCC is currently ongoing. ODAC recommended the study be completed and that side effects continue to be monitored.

However, patients may not need to wait until the study is completed. The FDA is expected to make a decision on whether to approve the drug later this month.

Pazopanib, like some of the other approved kidney cancer drugs, including Sutent, is an antiangiogenic. These drugs inhibit the growth of new blood vessels that feed the tumor by targeting the vascular endothelial growth factor receptor. Other kidney cancer drugs, including Afinitor, on the other hand, target a protein called mTOR.

Robert Figlin, MD, interim director of City of Hope Comprehensive Cancer Center in Duarte, California, and director of the center's kidney cancer program, told CURE earlier this year that, in addition to the recent kidney cancer drug approvals, there may still be more on the horizon.

"We are already embarking on next-generation drugs," he says, including pazopanib, and another angiogenesis inhibitor, axitinib. "Both of these may have more activity than our currently available drugs." They might also have a better side effect profile, he says. "That's what we're looking for--better tolerance and more effectiveness."

And the increase in the number of treatment options for kidney cancer patients has an added benefit.

"This is a waterfall time for patients," he says. "The challenges for both doctors and patients are now how to choose the proper drugs, in what sequence, and whether or not to use them in combination."

For more on kidney cancer advancements, read "Reining in Renal Cancer" from the Summer 2009 issue of CURE.

Rare lymphoma receives a much-needed drug approval

BY ELIZABETH WHITTINGTON | SEPTEMBER 28, 2009

Folotyn (pralatrexate), a drug which made waves after results of a phase II trial were revealed at last year's American Society of Hematology meeting, was granted accelerated approval for peripheral T-cell lymphoma on Friday. (You can read more about the PROPEL study from CURE's 2008 ASH coverage).

The approval is a first for PTCL, a rare and aggressive type of lymphoma that does not have many treatment options. The FDA based its decision on an improved overall response rate with the drug. While progression-free survival or overall survival (common endpoints in clinical trials) have not yet been demonstrated in a study, the improvement in response rate was enough for the FDA to give a green light to Folotyn because of PTCL's aggressive nature and lack of successful treatments. Additional studies of the drug will be ongoing to further assess clinical benefit.

The drug's manufacturer, Allos, has established a patient assistance program to help with reimbursement issues once the drug is available, which is projected to be early October. Patients can learn more about ASAP (Allos Support for Assisting Patients) by calling 877-272-7102 or visiting www.getASAPinfo.com.

Zevalin approved as first-line non-Hodgkin lymphoma therapy

BY ELIZABETH WHITTINGTON | SEPTEMBER 4, 2009

The approval of Zevalin (ibritumomab tiuxetan) as a first-line therapy for non-Hodgkin lymphoma was announced today. The drug was originally approved in 2002 for NHL patients whose cancer recurred or progressed after other therapies.

The new approval was based on a phase III study where patients whose cancer responded to first-line chemotherapy were given Zevalin. At 3.5 years follow-up, the group that received Zevalin as part of their first-line treatment had a significantly better median progression-free survival time than the control group (38 months compared to 18 months).

An antibody that contains a radioactive molecule, Zevalin works by delivering a lethal dose of DNA-damaging radiation to tumor cells. However, many NHL patients are only offered the drug as a last resort.

Bruce Cheson, MD, head of hematology and director of hematology research at Lombardi Comprehensive Cancer Center at Georgetown University, told CURE earlier this year that radioactive drugs, such as Zevalin and a similar drug, Bexxar (tositumomab), are some of the most effective NHL therapies on the market, but are also some of the least used. They are expensive (costing about $25,000 per treatment) and must be administered in a hospital under the supervision of a radiologist because of the drugs' radioactivity.

I'm not sure how Zevalin's most recent approval will help tackle the issue of cost and availability, but at least the option is now there for newly diagnosed NHL patients. An announcement on the drug's recent approval issued by the drug's manufacturer, Spectrum, mentioned that the company has plans to overcome these issues, which have plagued Zevalin since its original approval.

You can read more about Zevalin--and view an illustration on how the drug works--in Trying Something New from CURE's Spring 2009 issue.

The future of brain cancer therapy?

BY ELIZABETH WHITTINGTON | JULY 30, 2009

UCLA researchers have found a way to predict which brain cancers will respond to Avastin (bevacizumab), a drug recently approved for the disease (see Drugs in the News). By examining imaging scans of the brain, before Avastin is even administered, researchers can predict with 70 percent accuracy which tumors would respond (see images below).

The study focused on patients with glioblastoma, an aggressive form of brain cancer (read more on brain cancer in A Better Way to the Brain). Researchers looked at 82 patients treated with surgery and radiation. Half of the patients received Avastin every two weeks, and all patients had monthly MRI scans to monitor disease progression. By studying the MRI scans of patients whose disease recurred, they noticed something interesting.

Knowing how Avastin works helped investigators understand how they could use MRI to predict which tumors would best benefit from the drug. Avastin blocks the vascular endothelial growth factor (VEGF), a protein cancer cells secrete to signal blood vessel growth to tumors. VEGF can also cause blood vessles to leak fluid into and around the tumor, causing swelling and water movement (depicted by the wavy borders shown in photo 1). Because more water movement signaled higher VEGF levels, it made sense to the researchers that tumors with high VEGF levels would make excellent targets for Avastin.

Having the ability to predict who would respond to Avastin could potentially spare 50 percent of patients with recurrent glioblastoma the time, cost, and unnecessary side effects of a drug that wouldn't work, while providing them with other treatment options that may be more beneficial. Researchers say their next step will be to confirm the findings in a larger study.

You can read more about the study at http://newsroom.ucla.edu/portal/ucla/crystal-ball-for-brain-cancer-97149.aspx?link_page_rss=97149.

Good candidate for Avastin: Brain scan shows the wavy borders of a dying tumor in white at right. Dying cells leak fluid, causing swelling and water movement, which is linked to a good response to Avastin.

Bad candidate for Avastin: Brain scan shows the white mass of a solid tumor at left. The lack of water movement in the tumor and surrounding tissue suggests this tumor would not be a good candidate for treatment by Avastin.

Photo credits: UCLA/Pope lab