Study Confirms Adding Chemotherapy To Surgery Improves Survival In Advanced Gastric Cancer

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Disclaimer
Information contained in this press release was provided by the abstract's author and reflects the content of the study. It does not necessarily express ESMO's point of view

References

1. Abstracts from the 15th ESMO World Congress on Gastrointestinal Cancer are published in Annals of Oncology, Volume 24 suppls 4 June 2013 (Ann Oncol 2013 Jun; 24(Suppl 4): 5-130) http://annonc.oxfordjournals.org/content/24/suppl_4.toc

2. Abstract presentation: Thursday, 4 July 2013, 17:25 hrs, Session VII: Gastric Cancer About the ESMO World Congress on Gastrointestinal Cancer The ESMO World Congress on Gastrointestinal Cancer is the premier global event in the field, encompassing malignancies affecting every component of the gastrointestinal tract and aspects related to the care of patients with gastrointestinal cancer, including screening, diagnosis and the latest management options for common and uncommon tumours. It has been endorsed by leading professional societies and organizations.
The ESMO 15th World Congress on Gastrointestinal Cancer has been organized in partnership with ESMO (European Society for Medical Oncology). The Congress is developed and managed by ImedexR, LLC.

ABSTRACT 0007

Adjuvant capecitabine and oxaliplatin (XELOX) for gastric cancer after D2 gastrectomy: final results from the CLASSIC trial
Sung Hoon Noh 1, Sook Ryun Park 2, Han-Kwang Yang 3, Hyun Cheol Chung 1, Ik-Joo Chung 4, Kyung Hee Lee 5, Hyung-Ho Kim 6, Jiafu Ji 7, Jen-Shi Chen 8, Yunni Lim 9, Stella Ha 9, Yung-Jue Bang 3

1 Yonsei University College of Medicine, Seodeamungyu Shinchon-dong 134, Seoul, 2 Research Institute and Hospital, National Cancer Center, Ilsandong-gu, Goyang-si Gyeonggi-do, 3 Seoul National University College of Medicine, Jongno-gu, Seoul, 4 Chonnam National University Hwasun Hospital, Hwasun-Eup, Hwasun-Gun, Jeonnam, 5 Yeungnam University College of Medicine, Nam-gu, Daegu, 6 Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, 7 Beijing Cancer Hospital, Haidian, Beijing, 8 Chang Gung Memorial Hospital, Kwei-Shan Shiang, Taoyuan, 9 Roche Korea Co.,Ltd, Seocho-Gu, Seoul

Background: D2 gastrectomy, which is widely used in East Asia as the preferred surgery for patients with operable gastric cancer, is now recommended in US and European treatment guidelines for gastric cancer. Two phase III trials (ACTS-GC and CLASSIC) have been performed to assess the possible benefits of adjuvant chemotherapy after D2 surgery. ACTS-GC showed a survival benefit with fluoropyrimidine monotherapy after D2 gastrectomy compared with surgery only [Sasako et al. J Clin Oncol 2011;29:4387–93]. The CLASSIC trial compared fluoropyrimidine-oxaliplatin combination therapy (XELOX) with surgery alone; interim results showed that XELOX improved 3-year disease-free survival after D2 gastrectomy compared with surgery only [Bang et al. Lancet 2012;379:315–21]. Improved overall survival was also evident after only 3 years, but the data were immature. We report here the final results from the CLASSIC trial after a median follow-up of 5 years.

Methods: CLASSIC was a multinational open-label randomised phase III trial performed in South Korea, China, and Taiwan. Randomisation was stratified by country and disease stage. Patients with stage II–IIIB gastric cancer who had undergone curative D2 gastrectomy were assigned to adjuvant XELOX (oxaliplatin 130 mg/m2 day 1 plus capecitabine 1000 mg/m2 twice daily days 1-14 q3w) for 8 cycles or surgery alone. The primary endpoint was 3-year disease-free survival. The clinical cut-off date for the prospectively planned final 5-year efficacy analysis was 22 November 2012.

Results: At data cut-off, 103 (20%) patients in the XELOX group and 141 (27%) patients in the surgery alone group had died. This represented a 34% reduction in the risk of death with XELOX versus surgery alone (hazard ratio 0.66, 95% CI 0.51–0.85; p=0.0015 by stratified Cox regression analysis). The 5-year overall survival rate was 78% in the XELOX group and 69% in the surgery alone group (p=0.0029, log-rank test unstratified). 76 (15%) patients in the XELOX group and 135 (26%) patients in the surgery alone group received subsequent, non-protocol-specified anticancer therapies after progression of disease. In the analysis of disease-free survival, 139 (26.7%) patients in the XELOX group and 203 (39.4%) patients in the surgery alone group had relapsed, developed a new gastric cancer or died. This represented a 42% reduction in the risk of an event with XELOX versus surgery alone (hazard ratio 0.58, 95% CI 0.47–0.72; p<0.0001 by stratified Cox regression analysis). The 5-year disease-free survival rate was 68% in the XELOX group and 53% in the surgery alone group (p<0.0001, log-rank test unstratified).

Conclusion: The final analysis of the CLASSIC trial, after a median follow-up of 5 years, supports the findings from the primary analysis performed 2 years earlier. Adjuvant XELOX after curative D2 gastrectomy improves overall survival compared with surgery alone and should be considered as a standard treatment option for patients with operable gastric cancer.

ESMO

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

ESMO. "Study Confirms Adding Chemotherapy To Surgery Improves Survival In Advanced Gastric Cancer." Medical News Today. MediLexicon, Intl., 3 Jul. 2013. Web.
5 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

View the original article here

Autophagy Protects Neuroblastoma From Chemotherapy

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;??Pediatrics / Children's Health
Article Date: 03 Jul 2013 - 1:00 PDT Current ratings for:
Autophagy Protects Neuroblastoma From Chemotherapy

Neuroblastomas are pediatric tumors that originate from cells of the embryonic nervous system. The disease can take widely varying clinical courses that range from spontaneous regression to fatal outcomes. Highly aggressive neuroblastomas rarely respond well to chemotherapy. Understanding and overcoming the resistance mechanisms of highly aggressive neuroblastomas are considered essential to the development of effective treatments.

Scientists from the department headed by Professor Dr. Olaf Witt at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and at Heidelberg University Hospital are searching for more effective methods to treat neuroblastomas. The researchers are particularly focusing on the role of 18 different HDAC enzymes which appear to promote the aggressiveness of neuroblastomas in various ways. Dr. Ina Oehme and her colleagues from Witt's department have now studied whether a member of the HDAC family might be linked to the sensitivity of tumors to chemotherapy in high-risk neuroblastomas. She discovered that the high-risk tumors that responded well to therapy were those which had produced only small quantities of HDAC10 prior to treatment.

The Heidelberg researchers subsequently used an experimental agent or a method of blocking the gene to turn off HDAC10 experimentally in cell cultures developed from highly aggressive neuroblastomas. They subsequently treated the cells with the chemotherapy agent doxorubicin. In neuroblastoma cells, this treatment normally induces a self-digestion process known as autophagy, a kind of recycling of endogenous cellular components. This is a biologically ancient program for survival that protects cells during starvation. Highly aggressive cancer cells use autophagy to overcome stress caused by cytotoxic agents.

However, in neuroblastoma cells without a functioning form of HDAC10, treatment disrupted the multi-stage process of autophagy of cellular components at a specific point. As expected, these cells were once again rendered sensitive to the anticancer drug. The researchers cross-checked their results by boosting the activity of the HDAC10 gene in neuroblastoma cells. This protected the cells from the consequences of subsequent chemotherapy.

"HDAC10 appears to play a key role in autophagy and resistance to chemotherapy in high-risk neuroblastomas," Olaf Witt summarizes. "In advanced tumors, high levels of HDAC10 may serve as a biomarker for resistance. A drug that specifically turns off HDAC10 might give us a more effective method of treating neuroblastomas that respond very poorly to chemotherapy."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Ina Oehme, Jan-Peter Linke, Barbara C. Bock, Till Milde, Marco Lodrini, Bettina Hartenstein, Inga Wiegand, Christian Eckert, Wilfried Roth, Marcel Kool, Sylvia Kaden, Herrmann-Josef Grone, Johannes H. Schulte, Sven Lindner, Anne Hamacher-Brady, Nathan R. Brady, Hedwig E. Deubzer and Olaf Witt. Histone deacetylase 10 promotes autophagy-mediated cell survival. Proceedings of the National Academy of Sciences 2013, DOI: 10.1073/pnas.1300113110

The German Cancer Research Center (Deutsches Krebsforschungszentrum, D

Helmholtz Association of German Research Centres

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Helmholtz Association of German Research Centres. "Autophagy Protects Neuroblastoma From Chemotherapy." Medical News Today. MediLexicon, Intl., 3 Jul. 2013. Web.
5 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Autophagy Protects Neuroblastoma From Chemotherapy'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Sequential Chemotherapy Benefits Node-positive Breast Cancer Patients

Women with operable node-positive breast cancer experienced a survival benefit from sequential administration of doxorubicin, cyclophosphamide, and TaxotereR (docetaxel). These findings were recently published in The New England Journal of Medicine.[1]

Effective treatment of node-positive breast cancer often involves both local and systemic therapy. Local therapy consists of surgery and/or radiation and is directed at removing or destroying cancer cells in or near the breast. Systemic therapy is directed at destroying cancer cells throughout the body, and may include chemotherapy, targeted therapy, and/or hormonal therapy.

Anthracycline and taxane chemotherapy drugs are commonly used in the treatment of breast cancer. To compare three different approaches to administering chemotherapy, researchers conducted a study known as the National Surgical Adjuvant Breast and Bowel Project B-30 trial.

In this multicenter Phase III trial, 5,351 breast cancer patients with node-positive disease who had undergone total mastectomy or lumpectomy were randomized to receive eight cycles of treatment with sequential doxorubicin, cyclophosphamide, and Taxotere (ACT) over 24 weeks, concurrent TAC over 12 weeks, or a regimen of doxorubicin/Taxotere over 12 weeks.? In the concurrent TAC arm, all three drugs were administered together; in the sequential ACT arm, doxorubicin and cyclophosphamide were administered followed by Taxotere. After a median follow-up of six years, disease-free survival and overall survival were improved in the sequential ACT arm.

Overall survival was 83% in the sequential ACT arm, 79% in the concurrent ACT arm, and 79% in the doxorubicin/Taxotere arm.Disease-free survival was 74% in the sequential ACT arm, 69% in the concurrent TAC arm, and 69% in the doxorubicin/Taxotere arm.

The researchers concluded that sequential administration of ACT provided a statistically significant 17% reduction in mortality compared with doxorubicin/Taxotere and a nonsignificant 14% reduction in mortality compared with the concurrent TAC arm. In addition, patients who experienced amenorrhea (absence of menstrual bleeding) for six months or more experienced an improved overall survival in all arms of the study. ?The clinical significance of this finding is uncertain, but it of great interest and will lead to further investigation.? Studies are ongoing that continue to evaluate strategies to improve treatment for node-positive breast cancer patients.

Reference:

[1] Swain SM, Jeong J-H, Geyer CE, et al. Longer therapy, Iatrogenic amenorrhea, and survival in early breast cancer. New England Journal of Medicine. 2010; 362:2053–65.

View the original article here

Chemotherapy Effective Whether Given Before or After Breast Cancer Surgery

Giving chemotherapy before breast-conserving surgery is as effective against breast cancer recurrence as giving chemotherapy after breast-conserving surgery. These results were presented at the 2011 Breast Cancer Symposium.?

Breast-conserving surgery (also referred to as lumpectomy) involves removal of the breast cancer and some surrounding normal tissue. For some women, giving chemotherapy prior to surgery can shrink the cancer and make it easier to remove. There’s been some uncertainty, however, about whether chemotherapy followed by breast-conserving surgery is as effective against local-regional recurrence (cancer recurrence in or near the breast) as breast-conserving surgery followed by chemotherapy.?????

To evaluate whether risk of breast cancer recurrence varies by timing of chemotherapy, researchers collected information about roughly 3,000 women who underwent breast-conserving surgery and radiation therapy between 1987 and 2005. Roughly three-quarters of the patients underwent surgery first and the remaining patients underwent chemotherapy first. Women who received chemotherapy first tended to have cancers with worse prognostic features.????

Factors that were linked with an increased risk of breast cancer recurrence were young age (less than 50 years), clinical stage III cancer, grade 3 cancer, cancer that was estrogen receptor-negative, and close or positive surgical margins (cancer at or near the edge of the tissue that was surgically removed).?After accounting for tumor characteristics, risk of breast cancer recurrence was similar among women who underwent surgery first and women who underwent chemotherapy first.?

These results suggest that tumor characteristics—rather than the timing of chemotherapy—influence risk of breast cancer recurrence.?????

Reference: Mittendorf EA, Buchholz TA, Tucker SL et al. Impact of chemotherapy timing on local-regional failures in patients with breast cancer undergoing breast-conserving therapy. Paper presented at: 2011 Breast Cancer Symposium; September 8-10, 2011; San Francisco, CA. Abstract 82.?

Posted September 12, 2011

View the original article here

Herceptin Given At Same Time As Chemotherapy May Provide Most Benefit for Breast Cancer

The results of a Phase III clinical trial suggest that starting HerceptinR (trastuzumab) during chemotherapy for early-stage, HER2-positive breast cancer may be more effective than starting Herceptin after chemotherapy has been completed. These results were published in the Journal of Clinical Oncology.????

Fifteen to 20 percent of?breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Fortunately, the development of drugs such as Herceptin that specifically target HER2-positive cells has improved prognosis for women with HER2-targeted breast cancer.????

The optimal timing of Herceptin was evaluated in a Phase III clinical trial known as NCCTG N9831. The study enrolled women with Stage I-III HER2-positive breast cancer.? All women received chemotherapy with doxorubicin and cylophosphamide followed by paclitaxel, and some women also received Herceptin. Herceptin was started either at the same time as paclitaxel or later (after chemotherapy had been completed), and was given for a total of 52 weeks.????

Women who received both Herceptin and chemotherapy had a lower risk of cancer recurrence than women who received chemotherapy alone.?Women who started Herceptin at the same time as paclitaxel appeared to derive the most benefit. Five-year disease-free survival was 84.4% among women who received concurrent Herceptin and paclitaxel, compared with 80.1% among women who started Herceptin after finishing treatment with paclitaxel. This result did not meet the criteria for statistical significance, however, suggesting that it could have occurred by chance alone.?Starting Herceptin at the same time as paclitaxel did not appear to substantially increase the risk of side effects compared with starting Herceptin after chemotherapy had been completed.?

For women with early-stage, HER2-positive breast cancer, these results suggest that starting Herceptin during chemotherapy may produce better results than starting Herceptin after chemotherapy has been completed.?

Reference:?Perez EA, Suman VJ, Davidson NE et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. 2011;29:4491-4497.?

Posted December 4, 2011

View the original article here

Older Chemotherapy Regimen for Breast Cancer Linked with Persistent “Chemo Brain”

Women who received CMF chemotherapy for breast cancer between 1976 and 1995 scored slightly lower than women with no history of cancer on tests of word learning, memory, and information processing. These results were published in the Journal of Clinical Oncology.?

Studies of “chemo brain”—the foggy thinking and forgetfulness that patients may experience after chemotherapy—have suggested that the condition often improves with time. Some patients, however, may experience persistent problems.?

CMF is a chemotherapy regimen that was once commonly used in the treatment of breast cancer. It involves a combination of cyclophosphamide, methotrexate, and 5-fluorouracil. ?

To explore long-term effects of CMF on cognitive function, researchers in Europe conducted a study among 196 breast cancer survivors who had been treated with CMF between 1976 and 1995. The cognitive function of these women was compared with the cognitive function of more than 1,500 women who had never had cancer.?????

The cognitive test scores of the women who had been treated with CMF were slightly lower than the scores of the women who had never had cancer. Scores were lower in the areas of word learning, memory, and information processing speed. ?The reduction in test scores among the CMF-treated women was comparable to roughly six years of age-related cognitive decline.?

Although CMF is given less frequently than in the past, it is still used in some patients.? It is not known how other chemotherapy regimens affect long term cognitive function.? For women who are experiencing subtle but persistent cognitive problems, coping strategies—such as developing systematic daily routines and preparing well for activities such as work or travel—may be helpful.????

Some people appear to be more likely than others to experience long-term cognitive problems after chemotherapy, and researchers are looking into the reasons for this.?

Reference: Koppelmans V, Breteler MMB, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. Journal of Clinical Oncology. Early online publication February 27, 2012.?

Posted March 1, 2012

View the original article here

Herceptin and Chemotherapy Benefit Breast Cancer Patients with Brain Metastases

Among women with HER2-positive breast cancer that has spread to the brain, treatment with HerceptinR (trastuzumab) and/or chemotherapy can prolong survival. These results were published in Clinical Cancer Research.???

Although important advances have been made in breast cancer treatment, the treatment of metastatic breast cancer (breast cancer that has spread to other parts of the body) remains challenging. The brain is one area to which breast cancer may spread, and researchers continue to explore how best to manage patients with brain metastases.?????

To assess the frequency and outcome of brain metastases in women with metastatic HER2-positive breast cancer, researchers conducted a study among 1,023 newly diagnosed patients. HER2-positive breast cancer refers to cancer that overexpresses (makes too much of) the HER2 protein. Treatment of HER2-positive breast cancer often includes a HER2-targeted therapy such as Herceptin.???

Brain metastases were more common in younger women, those with hormone receptor-negative breast cancer, and those with a greater amount of cancer.?Among women who were free of brain metastases at the time of their initial diagnosis but later developed brain metastases, brain metastases were diagnosed a median of 13 months after initial diagnosis.?After the diagnosis of brain metastases, treatment with Herceptin and chemotherapy each significantly improved overall survival.??

These results suggest that even after HER2-positive breast cancer spreads to the brain, standard breast cancer treatments can prolong survival.?

Reference: Brufsky AM, Mayer M, Rugo HS et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clinical Cancer Research. 2011; 17: 4834–43.?

Posted July 20, 2011

View the original article here

Ovarian Suppression During Chemotherapy Fails to Improve Post-Treatment Menstrual Function

Among young women undergoing chemotherapy for breast cancer, use of the drug triptorelin to suppress ovarian function during treatment does not appear to improve post-treatment menstrual function. These results were published in the Journal of Clinical Oncology.???

Fertility preservation is increasingly being recognized as an important issue for young people with cancer. In premenopausal women, many chemotherapy drugs are toxic to the egg cells (oocytes) in the ovaries. If the number of remaining oocytes in the ovaries reaches a critically low point during treatment, women experience “acute ovarian failure.” This means that the ovaries stop functioning during or shortly after cancer treatment. If oocytes are lost during treatment but do not reach this critically low point, women are at risk for early menopause but may still be able to get pregnant for some time after treatment.????

Freezing embryos prior to cancer treatment is one of the most well established approaches to fertility preservation in young women, but is not always an option. One of the alternative approaches being evaluated involves the use of drugs known as gonadotropin-releasing hormone (GnRH) agonists to suppress ovarian function during chemotherapy. The hope is that this will protect the ovaries and improve post-treatment ovarian function.????

To explore the effects of the GnRH agonist triptorelin during chemotherapy for breast cancer, researchers conducted a study among premenopausal women age 44 or younger. Study participants were assigned to receive either triptorelin or a placebo. The study was originally designed to enroll 124 women, but it was stopped after only 49 women were enrolled because preliminary results indicated no benefit from triptorelin.????

Menstruation resumed in 88 percent of women in the triptorelin group and 90 percent of women in the placebo group.?Menstrual cycles resumed after a median of 5.8 months in the triptorelin group and 5.0 months in the placebo group.?

These results suggest that triptorelin does not improve post-treatment menstrual function in young breast cancer patients. Other, ongoing studies will provide more information on this topic.? ?

Premenopausal women who are interested in preserving their fertility during cancer treatment are advised to discuss their options with their physician before treatment begins.?????

Reference: Munster PN, Moore AP, Ismail-Khan R et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. Early online publication January 9, 2012.?

Posted January 13, 2012?

View the original article here