By Gene Emery
(Reuters Health) - 31/5/2019
In patients with locoregionally advanced nasopharyngeal carcinoma, adding gemcitabine and cisplatin induction to conventional treatment with platinum-based chemoradiotherapy increased the 3-year recurrence-free survival rate by 8.8 percentage points, according to results presented Friday at the American Society of Clinical Oncology's annual meeting in Chicago and online by the New England Journal of Medicine.
The open-label test studied 480 patients at 12 hospitals in China for a median of 42.7 months. Recurrence-free survival was 85.3% with three cycles of gemcitabine/cisplatin induction and 76.5% without (P=0.001).
Overall 3-year survival rates were 94.6% with gemcitabine/cisplatin pre-treatment versus 90.3% without.
But the rate of grade 3 or 4 side effects jumped by 20 percentage points with gemcitabine and cisplatin. The rates were 75.7% with the pre-treatment and 55.7% without. Neutropenia, thrombocytopenia, anemia, nausea and vomiting were the most common.
"This trial establishes induction chemotherapy plus concurrent chemoradiotherapy as the standard of care in locally advanced nasopharyngeal carcinoma," senior author Dr. Jun Ma, vice president at the Sun Yat-sen University Cancer Center in Guangzhou, China, told Reuters Health in an email.
Nasopharyngeal carcinoma affects about 130,000 people worldwide, often in North Africa, Southeast Asia and South China. Most people are diagnosed with locoregionally advanced disease. The disease kills about 70% of its victims.
In the new study, none of the patients had received previous cancer therapy. Gemcitabine was given on days 1 and 8 over a 3-week cycle for 3 weeks. Cisplatin was given on day 1 of each cycle. Nearly 97% of the 242 patients in the induction group completed all three cycles of induction therapy.
Dr. Ma said the improvement in the induction therapy group reflects a big advance because the jump in recurrence-free survival from 76.5% to 85.3% is "not the most appropriate indicator of the treatment effect."
"When you look carefully at the survival curves, you can see the two groups continue to separate after 3 years. Thus, the difference is (likely) to be even bigger with longer follow-up," he said. "Our results showed a hazard ratio of recurrence or death of 0.51, which meant that the risk was reduced by 49%. Thus, this is certainly a big jump to achieve our ultimate goal: making nasopharyngeal carcinoma history."
In addition to more serious adverse events with the added treatment, 13% had a reduction of gemcitabine or cisplatin because of hematologic side effects.
But Dr. Ma said patients will think the higher side effect rate is a small price to pay "because the new treatment increased the possibility of cure."
"It would be important to tell patients that not all serious (grade 3 or 4) side effects are created equal," he wrote. "For example, the major increased acute side effects in our trial were hematological, including neutropenia, thrombocytopenia, and anemia. Most of these side effects were discovered by laboratory tests only and most patients have no symptoms. Moreover, most acute side effects were temporary and reversible. Thus, such side effects would not significantly impair the patients' quality of life."
"What's more important to patients' long-term quality of life is late side effects, which are likely to be persistent or even permanent," said Dr. Ma. "We are glad to see that the incidence of late side effects was not increased with the induction chemotherapy, with the exception of mild peripheral neuropathy."
The patients will be followed for a median of 5 years.
N Engl J Med 2019.