ASCO: Pemetrexed Doublet Better for Quality of Life in Advanced NSCLC

CHICAGO, June 5 -- Pemetrexed (Alimta) plus platinum chemotherapy for advanced non-small cell lung cancer (NSCLC) may reduce toxicity compared with a gemcitabine (Gemzar) and platinum doublet but hold little other advantage.
In a Norwegian trial, leukopenia, granulocytopenia, thrombocytopenia, and transfusions were significantly less common with the pemetrexed combination, found Bjørn Henning Grønberg, M.D., of St. Olavs University Hospital in Trondheim, Norway, and colleagues.
However, health-related quality of life and overall survival were similar for the two first-line treatment regimens, Dr. Grønberg reported at the American Society of Clinical Oncology meeting here.
Phase II trials had suggested pemetrexed plus a platinum was as effective as standard doublets but with less toxicity as first-line NSCLC treatment, he said.
So they hypothesized that "less toxic treatment might provide better quality of life for patients who often have poor performance status and significant comorbidity."
Their multicenter, phase III trial therefore looked at the two regimens primarily from a quality-of-life standpoint among 437 patients with stage IIIb or IV NSCLC (28% to 29% and 71% to 72%, respectively).
Patients were randomized to receive four cycles every three weeks of 500 mg/m2 pemetrexed and carboplatin (Paraplatin) on day one, or 1000 mg/m2 gemcitabine on days one and eight plus carboplatin on day one.
All patients received supplemental vitamins. Those who were age 75 or older (18%) received 75% of the full doses.
The majority of patients in both groups tolerated all four doses (72% in the pemetrexed group and 62% in the gemcitabine group).
Quality of life, the primary endpoint, was measured with questionnaires at baseline, before every cycle, three weeks after the last cycle, and then every two months until one year after randomization.
Global quality-of-life scores were similar between groups at every point.
Subscales measuring nausea and vomiting, dyspnea, and fatigue also showed no statistically significant differences between treatment regimens.
Overall survival likewise was similar at a median of 220 days after randomization with the pemetrexed doublet and 210 with the gemcitabine doublet (P=0.60), the researchers found.
There were some significant differences in toxicity, though. Comparing pemetrexed- and gemcitabine-based therapy, their findings included:
Lower rates of grade three and four leukopenia with pemetrexed (17% versus 35% and 5% versus 9%, P<0.001).
Lower rates of grade three and four granulocytopenia with pemetrexed (24% versus 25% and 14% versus 23%, P=0.03).
Lower rates of grade three and four thrombocytopenia with pemetrexed (13% versus 31% and 11% versus 23%, P<0.001).
Lower rates of blood transfusion with pemetrexed (28% versus 42%, P=0.003).
Lower rates of platelet transfusion with pemetrexed (3% versus 9%, P=0.007).
It is not unprecedented that toxicity differences alone would compel oncologists to choose one regimen over another, the researchers noted.
"Carboplatin is often used in palliative treatment because of better tolerability and easier administration than cisplatin," Dr. Grønberg said.

ASCO: No NSCLC Survival Benefit with Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy did not improve survival of patients with resectable non-small cell lung cancer (NSCLC) compared with surgery alone, researchers reported here.
The trial, which is the largest one of its kind to date, was powered to detect a 15% improvement in overall survival but the five-year survival was 44% in the chemotherapy plus surgery group versus 45% for surgery alone, said Marianne Nicolson, M.D., of the Aberdeen Royal Hospitals Trust in Aberdeen, Scotland, and colleagues.
Despite the lack of overall benefit, Dr. Nicolson said that neoadjuvant chemotherapy should still be considered for a select group of patients who could benefit from pre-surgical staging or patients in whom co-morbidities might delay adjuvant chemotherapy. The study was published simultaneously online in The Lancet.
The trial recruited 519 patients -- 61% stage 1, 31% stage II, and a little over 7% stage III at centers in Great Britain, the Netherlands, Germany, and Belgium. Patients were enrolled from July 1997 to July 2005; 258 were randomized to neoadjuvant chemotherapy and 261 to surgery alone.
Patients were assigned to one of six platinum-based regimens: Mitomycin (Mutamycin), vinblastine (Velban), and cisplatin (Platinol); mitomycin, ifostamide (Mitoxana), and cisplatin; cisplatin and vinorelbine (Navelbine); paclitaxel (Taxol) and carboplatin (Paraplatin); cisplatin and gemcitabine (Gemzar); or docetaxel (Taxotere) and carboplatin.
Surgery was recommended as soon as possible after randomization for those in the surgery-only group and four to six weeks after the last cycle of chemotherapy for patients in the chemotherapy arm.
Among the findings:
75% of patients randomized to neoadjuvant chemotherapy completed all three cycles.
Partial or complete response was achieved in 49% of chemotherapy patients.
About 20% of chemotherapy patients had evidence of downstaging.
Only 2% of chemotherapy patients had progressive disease.
Complete resection was achieved in 79% of the surgery patients and 81% of neoadjuvant chemotherapy patients.
"We can say that neoadjuvant chemotherapy had absolutely no effect on disease-free progression or overall survival," Dr. Nicolson said.
During the discussion Dr. Nicolson was asked about the high rate of brain metastases among the chemotherapy patients -- 21 patients versus 10 patients in the surgery arm.
She said that the investigators found that "surprising, but we don't really think that it is evidence of biologic effect. We cannot at this time fully explain it."
Roman Perez-Soler, M.D., chairman of oncology at Montefiore Medical Center and professor of medical oncology at Albert Einstein College of Medicine, said the findings "confirm what we have known: neoadjuvant chemotherapy does not add a survival benefit but is a good therapeutic option for patients based on lesion size and location."
Dr. Perez-Soler was not involved in the study.
In an accompanying comment in The Lancet, Frances Shepherd, M.D., and Penelope Bradbury, M.D., of University Health Network, Princess Margaret Hospital, and the University of Toronto in Canada, wrote that the study suggests that surgery should not be delayed by neoadjuvant chemotherapy.
"While a systematic review indicates a potential benefit from preoperative chemotherapy," they wrote, "the body of evidence to date favors postoperative chemotherapy."

Study Compares Late-Stage Lung Cancer Treatments

WEDNESDAY, March 21 (HealthDay News) -- After initial chemotherapy, radiation treatment may be better than surgery for patients with advanced non-small cell lung cancer, a European study finds.
About 80 percent of all lung cancers are non-small cell lung cancers. Of those, about 30 percent of patients have locally advanced stages IIIA or IIIB.
The new study, published in the March 21 issue of the Journal of the National Cancer Institute, included 579 patients with stage IIIA non-small cell lung cancer that had progressed to the point where it could not be completely removed by surgery. The patients had all received three cycles of platinum-based chemotherapy.
Of the patients who responded to the chemotherapy, 165 then received radiation treatment, and 167 had surgery.
The median survival time for patients treated with radiation was 17.5 months, compared to 16.4 months for those who had surgery.
The five-year survival rate was 15.7 percent for those who had surgery compared with 14 percent for those treated with radiation. While the survival rates were similar, radiation was the preferred treatment because of its lower rates of complications and death, the researchers concluded.
"These results are important, because several centers routinely use chemotherapy followed by surgery to treat patients with this stage of disease based on small randomized studies that showed that surgery alone in inferior to chemotherapy and surgery in stage IIIA patients," the study authors wrote.
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