HYPRO: Shorter RT Course No Better, Worse in Localized Prostate Cancer


“A randomized phase III trial found that a hypofractionated radiotherapy (RT) regimen was not superior to, but generally equivalent to a conventional RT scheme in men with localized prostate cancer. The study joins a growing body of literature on hypofractionation in this malignancy, generally showing that the shorter courses are a reasonable option.

“A low α-β ratio for prostate cancer has generated interest in hypofractionation, as it could increase the tumor dose without increasing toxicities. ‘Moreover, hypofractionated radiotherapy is delivered in fewer fractions, improving patients’ convenience, hospital logistics, and possibly reducing healthcare costs,’ wrote study authors led by Luca Incrocci, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.

“A study was presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago that found a hypofractionated regimen of 60 Gy in 20 fractions was noninferior to conventional RT. Another, presented this past January at the ASCO Genitourinary Cancers Symposium, again found a 60 Gy/20 fractions regimen was noninferior to conventional RT and to another hypofractionated regimen of 57 Gy/19 fractions.”

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Shorter Radiation Course Recommended for Early-Stage Breast Cancer Patients


“Early-stage breast cancer patients receiving a shorter course of whole breast radiation with higher radiation doses per fraction reported equivalent cosmetic, functional and pain outcomes over time as those receiving a longer, lower-dose per fraction course of treatment, according to researchers from The University of Texas MD Anderson Cancer Center.

“Their study, published in Cancer, found patient-reported functional status and breast pain improved significantly following both radiation schedules, and there were no significant differences in physician-reported cosmetic evaluations. With a more convenient treatment schedule and equivalent outcomes, the authors suggest the shorter course as the preferred option for patients.”

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Fewer, Larger Radiotherapy Doses Prove Effective for Prostate Cancer Patients

“Giving fewer but higher doses of radiotherapy, is as effective at treating prostate cancer as giving lower doses for a longer period, according to new research presented at the 2015 European Cancer Congress today (Monday).

“The results could mean men need fewer trips to hospital – over four weeks rather than seven and a half – without reducing the quality and impact of their prostate cancer treatment.

“The Cancer Research UK funded CHHiP trial – the largest randomised treatment trial ever undertaken in localised prostate cancer led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust – gave 3216 men with prostate cancer from across the UK different schedules of radiotherapy.”

Radiation Oncologist Advocates for Shorter Treatment with Higher Doses of Radiation in Early Breast Cancer

The gist: This is an opinion article written by a radiation oncologist. He believes that early-stage breast cancer patients should have shorter radiation treatments with higher doses of radiation.

“As healthcare professionals, we play an important role in evaluating oncology patients and providing information on the relevant treatment options. For women with early-stage breast disease, there are a variety of decisions to make regarding these options. For example, some women may be eligible for breast-conserving surgery, which typically includes a lumpectomy followed by radiation. Radiation treatment after a lumpectomy has traditionally involved irradiation of the entire breast with an external beam over 6 weeks. However, recent data suggest it may be time to break tradition.

“A recent study analyzed the frequency of hypofractionated whole-breast irradiation (WBI) versus conventional WBI after breast-conserving surgery in the U.S. from 2008 through 2013. Researchers defined hypofractionated treatments as those spanning 11 to 24 fractions over approximately 3 weeks and conventional fractionation as 25 to 40 treatments over approximately 6 weeks. It is important to address a common misconception about radiation treatments analyzed in this 5-year study. The radiation volume for patients undergoing hypofractionated and conventional whole breast irradiation are the same. However, the dosage per treatment is higher for hypofractionated, allowing a patient to receive the same total amount of radiation in a shorter time period. Both treatment types have the same effect on a cancer cell.

“The researchers found that the percentage of patients treated with hypofractionation increased from 10.3% to 34.5% over 5 years. Even so, a majority of eligible women still did not receive the shorter, more intense course of radiation therapy. This means that a majority of the women who were eligible to receive the same amount of radiation in just 3 weeks unnecessarily received a longer course of treatment. Besides the inconvenience of a lengthier regimen, many women must travel some distance to receive radiation. The additional 3 weeks of radiation can put additional stress on patients with work and family responsibilities.”

Moffitt Researchers Discover Mechanism Leading to Drug Resistance, Metastasis in Melanoma Patients

The gist: New research suggests that some melanoma patients might benefit from a treatment schedule that alternates BRAF inhibitor drugs with MEK inhibitor drugs. The scientists hypothesize that this schedule could help prevent drug resistance and metastasis. The researchers set out to figure out why patients who receive BRAF inhibitors develop more metastases than patients on standard chemotherapy. They found that unusually high activity of a protein called EphA2 on cancer cells may be the culprit. Taking away BRAF inhibitors seemed to lower the aggressiveness of these cells. So, periodically taking away BRAF inhibitors from patients might theoretically help stave off resistance and metastasis.

Moffitt Cancer Center researchers have discovered a mechanism that leads to resistance to targeted therapy in melanoma patients and are investigating strategies to counteract it. Targeted biological therapy can reduce toxicity and improve outcomes for many cancer patients, when compared to the adverse effects of standard chemotherapeutic drugs.  However, patients often develop resistance to these targeted therapies, resulting in more aggressive cells that can spread to other sites or cause regrowth of primary tumors.

“B-Raf is a protein that is frequently mutated in human cancers, leading to increased tumor cell growth, survival and migration.  Drugs that target B-Raf or another protein in the same network called MEK have proved effective in clinical trials. Several B-Raf and MEK inhibitors have been approved with the combination of a B-Raf and a MEK inhibitor being the current standard of care for patients with B-Raf mutant melanoma. However over time many patients become resistant to B-Raf and B-Raf/MEK inhibitor therapy.

“Moffitt researchers found that patients who are on B-Raf inhibitor drugs develop more new metastases than patients who are on standard chemotherapy. The researchers wanted to determine how this acquired resistance develops in order to devise better treatment options for patients. They found that melanoma cells that are resistant to B-Raf inhibitors tend to be more aggressive and invasive, thereby allowing the tumor to spread to a new organ site.  They used a large screening approach and discovered that this resistance and aggressive behavior was due to high activity of a cell surface protein called EphA2, which is also found on glioblastoma stem cells.”

Four Cycles of FEC Chemotherapy Are as Good as Six Cycles in Node-Negative Breast Cancer

The gist: A recent clinical trial showed that people with node-negative breast cancer did just as well on a shorter, four-week chemotherapy treatment as people who took a longer, six-week one. The shorter treatment consisted of four cycles of doxorubicin and cyclophosphamide. The longer one involved six cycles of 5-fluorouracil, epirubicin and cyclophosphamide. Patients in both groups had similar survival rates, and people in the longer treatment group had worse side effects.

“Patients with node-negative breast cancer who received six cycles of 5-fluorouracil, epirubicin and cyclophosphamide experienced similar DFS and OS as patients who received four cycles of doxorubicin and cyclophosphamide, according to results of a phase 3 study presented at the San Antonio Breast Cancer Symposium.

“ ‘[In the MA-5 trial, the NCIC Clinical Trials Group] administered a dose-intensified epirubicin program, and the RFS and OS results were encouraging,’ Charles Edward Geyer, Jr., MD, FACP, associate director for clinical research at Virginia Commonwealth University Massey Cancer Center, said during his presentation. ‘Additionally, the French Adjuvant Study Group around that time had also evaluated their standard adjuvant regimen of FEC-50 and had shown that six cycles of therapy were more effective than three. So, at that time, we had two separate trials looking at different epirubicin schedules, both of which had seemed to be positive. It seemed reasonable at that time to compare [doxorubicin and cyclophosphamide] with one of those regimens. Since we were going to conclude the study in node-negative patients and include post-menopausal women, we chose the FEC-100 [chemotherapy regimen] because of its improved toxicity profile…’

“ ‘[Six cycles of] FEC-100 did not improve the primary endpoint of DFS or our secondary endpoint of OS relative to [four cycles of] AC,’ Geyer said. ‘Toxicities were increased with the FEC-100, which wasn’t unexpected because it did administer additional cycles of therapy compared with AC. Overall, the results do not support the use of six cycles of anthracycline-based regimens in node-negative breast cancer.’ “

Weekly Paclitaxel or Docetaxel Every 3 Weeks Improves Survival in Breast Cancer

The gist: A different treatment schedule after surgery might increase survival and time without cancer worsening for women with axillary node-negative or high-risk node-negative breast cancer. A clinical trial found that these women might benefit from taking the drug paclitaxel once per week or docetaxel once every three weeks, instead of paclitaxel once every three weeks. The same trial found that women with triple negative breast cancer (TNBC) also benefit from weekly paclitaxel. But docetaxel once every three weeks showed better results for women with ER-positive, HER2–negative breast cancer.

“Women with axillary node-negative or high-risk node-negative breast cancer achieved prolonged DFS and marginally improved OS when they received adjuvant paclitaxel every week or docetaxel every 3 weeks compared with paclitaxel every 3 weeks, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

“Further, weekly paclitaxel extended DFS and OS in women with triple-negative breast cancer, whereas docetaxel administered every 3 weeks improved DFS in women with ER-positive, HER-2–negative disease.

“Joseph A. Sparano, MD, professor of medicine and women’s health at Albert Einstein College of Medicine, and colleagues evaluated various regimens in 4,954 women with axillary node-positive or high-risk node-negative breast cancer. Previously released results, based on a median 5.3 years of follow-up, showed those who received adjuvant weekly paclitaxel (HR=0.73; P=.0006) or docetaxel every 3 weeks (HR=0.77; P=.02) demonstrated longer DFS than women who received paclitaxel every 3 weeks.

“The current analysis occurred after a median 12.1 years of follow-up. The numbers of DFS events (1639 vs. 1048) and deaths (1283 vs. 686) in the current analysis vs. the previous report were substantially higher.”

Briefer Biochemotherapy Yields Better Relapse-Free Survival but Greater Toxicity vs 1-Year High-Dose Interferon in High-Risk Melanoma

The gist: Compared to a standard treatment, an alternative, shorter treatment for stage III melanoma may lengthen the amount of time patients go without their cancer returning. However, it has more toxic side effects. And compared to the standard, it doesn’t lengthen life. The alternative treatment uses the drugs cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b. In a clinical trial with volunteer patients, it was compared to longer (1-year), high-dose treatment with the drug interferon alfa-2b. The trial involved people aged 10 years and older with stage IIIA-N2a through IIIC-N3 melanoma.

“In a phase III trial (Southwest Oncology Group Intergroup S0008) reported in the Journal of Clinical Oncology, Flaherty et al found that a shorter course of biochemotherapy consisting of cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b produced better relapse-free survival, but not overall survival, and was associated with greater toxicity compared with a 1-year high-dose interferon alfa-2b regimen in patients with high-risk melanoma. The trial is a Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group Intergroup study…

“In the trial, 402 patients aged ≥ 10 years with stage IIIA-N2a through IIIC-N3 melanoma were randomly assigned between September 2000 and November 2007 to receive biochemotherapy plus granulocyte colony-stimulating factor given every 21 days for three cycles (n = 199) or high-dose interferon alfa-2b intravenously 5 days per week for 4 weeks and subcutaneously three times per week for 48 weeks (n = 203). The coprimary endpoints were relapse-free survival and overall survival.

“The high-dose interferon and biochemotherapy groups were generally balanced for age (median, 48 and 46 years), sex (69% and 71% male), race/ethnicity (96% and 95% white), number of involved nodes (1–3 or satellite/in-transit only in 76% in both), nodal involvement (micrometasteses only in 43% and 44%), and ulceration (41% in both)…

“The investigators concluded: ‘Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in [relapse-free survival] but no difference in [overall survival] and more toxicity compared with [high-dose interferon].’ ”

Emesis Combo Quells CINV in Three Trials (CME/CE)

The gist: Some cancer patients who are treated with chemotherapy experience nausea and vomiting as side effects. Researchers recently conducted three clinical trials with volunteer patients to test a treatment for chemotherapy-induced nausea and vomiting (CINV). The trials compared two different dosing schedules of a treatment that combines the drugs netupitant and palonosetron (aka Aloxi). The researchers reported that a single-dose schedule solved the CINV problem for more patients than a multidose schedule.

“A single-dose antiemetic regimen provided superior control of chemotherapy-induced nausea and vomiting (CINV) as compared with a standard multidose regimen, according to results of three randomized trials.

“In each trial, the fixed-dose combination of netupitant and palonosetron (Aloxi) led to a significantly higher rate of complete response during the delayed phase of the first cycle of chemotherapy versus control regimens. Complete response rates with netupitant-palonosetron (NEPA) regimen ranged from 76% to 89%, representing absolute differences of 5% to 14% versus the control groups.

“Taken together, results of the three trials suggest a ‘winning team’ in the search for optimal management of CINV, reported Matti Aapro, MD, of the Multidisciplinary Oncology Institute in Genolier, Switzerland, and colleagues in the July issue of Annals of Oncology.

” ‘If the present registration trial results are replicated in the “real” clinical world, then the NEPA formulation appears to be an advance in terms of overall efficacy and simplicity of dosing regime with the maintenance of efficacy over multiple cycles of chemotherapy being particularly encouraging,’ Paul L.R. Andrews, PhD, of St George’s University of London, said in an accompanying editorial.”