Preliminary clinical results with gemcitabine, an investigational
difluoronucleoside, were presented during scientific sessions
organized by the 7th World Conference on Lung Cancer, which was
held in Colorado Springs last year. The agent produced promising
response rates in patients with non-small-cell lung cancer (NSCLC),
in both single-agent and combination chemotherapy trials.
The research presentations and posters at the meeting focused
on data from completed phase II clinical trials in Europe, Japan,
and Canada in which gemcitabine had been given to patients with
Two multicenter phase II studies were conducted to determine the
clinical efficacy of gemcitabine for the treatment of non-small-cell
lung cancer. The first study evaluated 151 patients with inoperable
NSCLC. Gemcitabine, 1,250 mg/m², was administered as a 30-minute
intravenous infusion once a week for 3 weeks followed by 1 week
of rest. This constituted one treatment cycle.
The results of the trial indicated an overall response rate of
22%, which included 3 complete and 30 partial responses. According
to the lead investigator, Ulrich Gatzemeier, MD, Grosshansdorf
Hospital, Germany, this response rate compares favorably with
single-agent response rates reported in the medical literature
for other existing drugs used against lung cancer. Similar response
rates were reported in two independent Japanese studies enrolling
a combined 136 patients with previously untreated NSCLC, of which
116 were evaluable at the time. The dosing schedule was comparable
to that used in the European study, although the initial gemcitabine
dose was 1,000 mg/m², with allowance made for increasing
the dose to 1,250 mg/m², depending on the patients' tolerance
levels during the first cycle. An overall response rate of 23%
Both studies showed gemcitabine to be generally well tolerated.
Overall, the most common side effects reported were neutropenia
in the first study and leukopenia, anemia, loss of appetite, and
fatigue in the second study. Gemcitabine's "overall mild
toxicities, in particular, modest myelotoxicity, may warrant further
investigation of this drug in combination with other anticancer
agents," said lead investigator Yushi Nakai, MD, of the Sendai
Kousei Hospital in Japan.
Preliminary results from two phase I combination studies involving
gemcitabine and cisplatin to treat NSCLC were also presented at
the Colorado conference.
One study was conducted to determine the maximum tolerated doses
of a 4-week cycle of gemcitabine and cisplatin when administered
for 3 weeks, with a 1-week rest period. The starting dose of gemcitabine
was 1,000 mg/m² for 3 weeks. At the next dose level, only
cisplatin was increased to 30 mg/m² per week for 3 weeks.
Thereafter, dose escalations were made only for gemcitabine (to
1,250 mg/m² and 1,500 mg/m²). At the time of the conference,
25 patients (24 eligible) had been entered in the study. The initial
partial response rate for this study was 7 out of 12 patients.
Similar results were reported in a second phase I dose-escalation
study of gemcitabine in combination with cisplatin, using a different
dosing schedule. In 15 patients, gemcitabine 1,000 mg/m²
was administered as a 30-minute IV infusion on days 1, 8, and
15 of a 28-day cycle. On day 15, cisplatin was given immediately
after gemcitabine administration at the following dose levels:
60 mg/m² (3 patients), 75 mg/m² (3 patients), and 100
mg/m² (9 patients). For these patients, gemcitabine did not
add to expected cisplatin toxicity. The most commonly noted side
effects included neutropenia, thrombocytopenia, transient rise
in liver function tests, nausea, and vomiting. The number of evaluable
patients with response rates was two out of three at the 60-mg/m²
cisplatin dose level, none out of three at 75 mg/m², and
four out of four at 100 mg/m².
Based on the findings of these two studies, The Toronto Hospital's
Frances A. Shepherd, MD, one of the lead investigators, said,
"The preliminary response data suggest that the gemcitabine
and cisplatin [combination] is an active regimen against NSCLC.
It is well tolerated and deserves further study in comparison
with other chemotherapy combinations."
Lung cancers are among the most difficult cancers to treat. An
effective therapy for advanced NSCLC, which accounts for nearly
75% of all lung cancer cases, has been particularly elusive. The
5-year survival rate for those with NSCLC stands at less than
Gemcitabine is being tested by Eli Lilly and Company, which has
applications pending for regulatory approval of this compound
in 19 countries outside the United States for the indication of
non-small-cell lung cancer. The drug is also being studied for
the treatment of pancreatic cancer in an ongoing US registration
trial. Data also suggest that gemcitabine may have activity against
other solid tumors, including breast, ovarian, bladder, and prostate
cancers. Further studies with these tumors are planned to confirm
the activity of the compound.