Chemo: combinatie chemo met Navelbine,- cisplatin en vinorelbine geeft bij longkankerpatiënten (stadium I en II) positief effect op vijf jaars overleving blijkt uit 10 jarige gerandomiseerde placebo gecontroleerde fase III studie bij 482 patiënten.

10 juli 2011: onderstaande studie is een van de weinige studies die aantoont dat chemo effectief zou zijn bij operabele longkanker stadium I en II als post operatieve behandeling. Inmiddels is uit vele andere studies gebleken dat andere middelen en aanpak effectiever en met minder bijwerkingen longkanker kunnen bestrijden. Toch laat ik deze studie staan omdat deze is vergeleken met niets doen, placebo. En dan blijkt het verschil op de 5-jaars overleving slechts 6% tot 8% en dus helemaal niet zo echt heel veel groter.

Findings

367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17—108] vs 59% [17—100]). After a median follow-up of 76 months (range 43—116), median survival was 65·7 months (95% CI 47·9—88·5) in the chemotherapy group and 43·7 (35·7—52·3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0·80 [95% CI 0·66—0·96]; p=0·017). Overall survival at 5 years with chemotherapy improved by 8·6%, which was maintained at 7 years (8·4%).

Het volledige studieverslag kunt u opvragen bij The Lancet. Klik daarvoor op deze deeplink: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB—IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association ): a randomised controlled trial

Een persoonlijke opmerking hierbij: zouden al die mensen die geld geven aan het KWF zich wel realiseren dat het overgrote deel van hun geld naar dit soort onderzoek gaat en niet naar onderzoek van effecten van goede niet toxische zorg en middelen?

23 juni 2005: Bron: DOW met dank aan Karel

Hoewel altijd is verondersteld, (althans dat staat nu in verklaring bij dit studiebericht, maar we vermoeden dat vele longkankerpatienten afgelopen jaren vaak te horen hebben gekregen dat chemo wel degelijk efectief zou zijn en een kans op genezing zou zijn, maar ja artsen moeten het ook een beetje verkopen natuurlijk), dat chemo bij longkanker weinig tot geen effect heeft op uiteindelijke overleving melden onderzoekers nu dat een behandeling met een combinatie chemo van cisplatin en vinorelbine onder de naam Navelbine wel voor een beter resultaat zorgt. Een gerandomiseerde studie bij 482 longkankerpatiënten met niet-klein-cellige vorm en stadium I en II, dus nog geen uitzaaiingen wijst uit dat de vijfjaars overleving bij deze groep en deze behandeling gaat naar 69%. Opmerkelijk is wel dat zowel in het abstract als in een persbericht van de Wallstreet Journal niet de cijfers van de gerandomiseerde groepen naast elkaar worden gelegd, maar het resultaat van 69% vijf jaars overleving naast dat van een statistisch cijfer. Ook is opmerkelijk dat Canadese longkankerpatiënten die meededen aan de studie het opmerkelijk slechter deden dan Amerikaaanse deeelnemers. Daarvoor wordt geen verklaring gegeven. Leest u achtereenvolgens het abstract en een persbericht over deze studie kritisch. Volgens ons is dit niet zo'n jubelend resultaat als waarmee het naar buiten wordt gebracht.

Lung Cancer. 2005 Mar;47(3):385-94

Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature.

Alam N, Shepherd FA, Winton T, Graham B, Johnson D, Livingston R, Rigas J, Whitehead M, Ding K, Seymour L.
National Cancer Institute of Canada-Clinical Trials Group, 10 Stuart Street, Kingston, Ont., Canada K7L3N6.

Resected non-small cell lung cancer (NSCLC) has 5-years survival rates of 30-70%. The role of adjuvant chemotherapy remains unclear with poor compliance reported in most trials. The compliance with adjuvant chemotherapy (ACT) for stage IB and II NSCLC was analyzed using data from a North American multi-centre phase III study (accrual 1994-2001) that compared adjuvant chemotherapy to observation. Planned chemotherapy consisted of cisplatin (CIS) 50 mg/m2 days 1, 8 and vinorelbine (VIN) 25 mg/m2 days 1, 8, 15, 22 for four cycles; the VIN dose had been reduced from 30 mg/m2 after an initial cohort of patients experienced unacceptable toxicity. Four hundred and twenty-four patients were randomized after the amendment, 215 to the chemotherapy arm. Median age was 60 years, 64% were male and 84% had stage II disease. Thirty-seven patients completed one cycle, 14 completed two, 20 completed three and 108 patients completed all four cycles. Ten patients received no therapy. Multivariate analysis demonstrated statistically significant differences in compliance with extent of surgery, gender and age. Patients randomized in Canada were more likely to fail to complete chemotherapy due to refusal of therapy than their American counterparts. Patients who had pneumonectomies were more likely to discontinue therapy due to toxicity than those who had lesser resections. Extent of surgery may play a role in both the compliance and toxicity of ACT. Differences between nations in the perception of the risks and benefits of adjuvant chemotherapy regimens, both between physicians and patients, should be investigated further.

PMID: 15713522 [PubMed - in process]

-- WSJ(6/23) A Major Shift In Treating Lung Cancer -- (From THE WALL STREET JOURNAL) By Keith J. Winstein
,br> IN A FINDING that is altering the standard of care for early-stage lung-cancer patients, a study says chemotherapy greatly improves their chances of survival. Lung cancer is by far the leading cancer killer, responsible for about 165,000 deaths a year in the U.S., exceeding those from colon, breast, pancreatic and prostate cancer combined. The standard treatment for early-stage lung cancer has long been surgery to remove the lobes containing the tumor. But even then, only about 54% of patients survive beyond five years. With many other cancers, such as colon, breast and ovarian, chemotherapy is added to surgery to improve survival rates. But no published studies had shown a substantial benefit from chemotherapy after surgery for early-stage lung-cancer patients, who represent nearly a third of all cases.
Now, final results of a 10-year trial of 482 patients with early-stage lung cancer show that intravenous chemotherapy drugs improved five-year survival rates to 69%. That 15-point improvement was described by several doctors as surprisingly strong. Previous studies had failed to demonstrate any more than a four-point benefit from follow-on chemotherapy, making doctors and patients reluctant to opt for the chemotherapy, which sometimes requires hospitalization. "There's never been a lung-cancer trial that showed this benefit of treatment in any stage of disease," said Katherine M.W. Pisters, an oncologist at the University of Texas M.D. Anderson Cancer Center in Houston, who wasn't involved in the study. The study, which was conducted in Canada and the U.S., is good news only for the 30% of lung-cancer patients whose cancers are discovered in the early stages. That is about 50,000 Americans each year. Publication of the research in today's issue of the New England Journal of Medicine is expected to drive more doctors who have resisted recommending chemotherapy in the past to now do so -- despite unpleasant side effects that include nausea, fatigue and diarrhea. And in response to the findings, the American College of Clinical Oncology and the American College of Chest Physicians are rewriting their official guidelines to physicians to recommend chemotherapy for early-stage lung-cancer patients. Dr. Pisters, who is in charge of both groups' efforts, says preliminary findings of the study, which came out last year, have already begun to change the care for early-stage patients. The picture for lung-cancer patients overall, almost all of whom are smokers or former smokers, remains dire, even by cancer standards. Since there is no systematic screening for lung cancer, unlike breast and colon cancer, about 40% of the 173,000 new cancer cases each year aren't discovered until the cancer is metastatic, or spreading. At that point, it's essentially too late to have a chance for survival, according to Alan B. Sandler, the medical director of thoracic oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., who wasn't involved in this new research. Only about 15% of lung-cancer patients overall survive beyond five years. "A lot of people in lung cancer are still somewhat resistant" to adding chemotherapy, says Dr. Sandler, noting that some doctors have the attitude, "Oh, it's a bunch of smokers. They're too sick, they're too old." With the new research, he said, "the nihilism toward lung cancer is slowly starting to diminish." Timothy Winton, the University of Alberta doctor who led the study, says that recent advances -- better chemotherapy drugs as well as better treatments for the side effects of high doses -- have greatly advanced the state of the art. In the $4 million randomized trial of 482 patients with early-stage lung cancer, researchers used a four-month regimen of intravenous chemotherapy with the drugs cisplatin and vinorelbine, which is also known as Navelbine. Both are available generically. Begun in 1994, the study was funded by the American and Canadian governments' National Cancer Institutes, and received $1.6 million from GlaxoSmithKline PLC, which used to hold the exclusive rights to vinorelbine in North America until the patent expired a few years ago. A GlaxoSmithKline spokeswoman described the company as thrilled that the research had turned out positively but disappointed the results hadn't arrived until after its patent had expired. The company no longer actively markets vinorelbine, she said. Frances A. Shepherd of the University of Toronto, a senior author on the study, said a forthcoming analysis of the study's patients will show that despite side effects, "within a few short months after chemo, the quality of life levels had come up to the baseline" of nonchemotherapy patients. For some doctors, the preliminary results released last year were already changing the conversation between doctors and patients. Just a few years ago, Dr. Pisters said, her patients would tell her that if chemotherapy makes only a small difference, then, "I don't want it." But now, "the conversation is completely different," she said. "I look people in the eye and say, `If you take chemotherapy, we can reduce your risk of death by 30%." Previously, less than 20% of her patients opted for chemotherapy, Dr. Pisters said. Now more than 90% do. Doctors at the University of Toronto have done a follow-on study of the impact of the U.S./Canada research on Toronto's surgeons and patients. After the announcement in 2003 of research showing a four-point benefit from chemotherapy, only about 10% of early- and midstage patients were referred for and received chemotherapy. But since Dr. Winton announced his preliminary results a year ago, the number of referrals jumped to 62% -- and of those, every single patient opted to receive chemotherapy. Those results will be presented at next month's meeting of the World Conference on Lung Cancer in Barcelona, said Natasha Leighl, an oncologist at the university. --- Some estimated annual lung-cancer statistics in the U.S. Patients diagnosed: 172,570 Deaths from lung cancer this year: 163,510 Number of patients found at an early stage: 50,000 Early-stage patients who would survive five years with surgery alone: 28,000 Early-stage patients who would survive if all received chemotherapy: 35,700 Sources: American Cancer Society, New England Journal of Medicine

longkanker, vinorelbine, cisplatin