In October 1999, 40 leading experts from Europe,
the United States, and the Far East met in St. Julians, Malta, to
discuss recent progress in the management of lung cancer. Emphasis
was placed on novel treatment strategies for nonsmall-cell
tumors, including combination chemotherapy and combined-modality treatment.
Gemcitabine (Gemzar) is approved as primary therapy for advanced
nonsmall-cell lung cancer (NSCLC) in several countries
worldwide. Expanded use of gemcitabine and the evolving role of
Alimtaa multitargeted antifolate (MTA)were the major
focal points for data review and discussion. Other agents with
appealing activity, such as oxaliplatin, were also discussed.
Both gemcitabine and Alimta offer substantial single-agent activity
in NSCLC. Several new gemcita-bine doublets are being widely tested,
and randomized phase II and phase III trials involving these
gemcitabine regimens are also now underway. Preliminary results of
some of these trials, as well as their implications, were presented
and considered at this conference. The developing combination of
gemcitabine and Alimtaa regimen with preclinical evidence of
synergywas of particular interest.
Multiple-induction chemotherapy studies report excellent response
rates for gemcitabine and cisplatin (Platinol) as initial therapy in
patients with stage III NSCLC. Now, a multicenter trial in Italy
is comparing induction therapy with this combination followed by
surgery vs surgery alone. A similar design in the United States will
study induction therapy with carboplatin (Paraplatin) and paclitaxel
(Taxol) followed by surgery vs immediate surgical resection. In
Spain, a three-arm trial is currently underway, comparing surgery
alone vs induction chemotherapy followed by resection vs resection
followed by adjuvant chemotherapy.
The radiosensitizing potential of gemcitabine is well recognized.
Initial attempts to combine full doses of weekly gemcitabine with
curative radiotherapy for patients with locally advanced NSCLC were
associated with unacceptable in-field toxicity. However, additional
studies using different treatment volumes, fractionation schedules,
and chemotherapy doses are needed to define a safe and beneficial
interaction between these two active modalities. For example, Vokes
et al recently completed a Cancer and Leukemia Group B trial in
patients with stage III NSCLC. Results of this study demonstrate the
feasibility and tolerability of induction chemotherapy with a
standard gemcitabine/cisplatin combination followed by concurrent
radiation plus a reduced dose and less frequent schedule of gemcitabine.
Data from several studies of Alimta were also presented, and the
future development of this agent was discussed. Alimta offers
substantial single-agent activity in lung cancer. It also offers
theoretical appeal in terms of overcoming de novo or developing drug
resistance, because of its multiple sites of cellular action.
Conference members also reviewed the status of the development of
Alimta combinations and suggested further studies. In particular, the
evaluation of gemcitabine/Alimta combinations as first-line therapy
was considered a priority. The potential for Alimta as second-line
therapy for previously treated patients with NSCLC was also of interest.
Different treatment approaches in Europe, the United States, and the
Far East were articulated by conference participants. Standard
care approaches in the United States and Europe were also
discussed. Of debate was whether there is a well-defined
standard chemotherapy for locally advanced or metastatic
NSCLC. Clearly, in the United States, the dominant combination is
carboplatin/paclitaxel, despite the absence of randomized data to
suggest this combination is more efficacious than numerous other
available regimens. In Europe and Canada, gemcitabine/cisplatin and
vinorelbine (Navelbine)/cisplatin are widely used, with country by
country differences quite evident.
Based on the completed studies of the North American cooperative
groups, treating physicians in the United States often use an
induction strategy of concurrent chemoradiation followed either by
surgery or additional radiation in appropriate patients with stage
III disease. Response rates are high with the use of concurrent
chemoradiation, but acute toxicity is increased and surgical and
postoperative care may be rendered more challenging.
In much of Europe, induction chemotherapy alone followed by
definitive locoregional treatment is the more common approach.
However, the addition of a component of concurrent chemoradiation is
certainly being tested. Conference members debated the relative
values of these strategies and opportunities for additional testing
to optimize the overall approach.
We look forward to continuing this dialogue with an expanding circle
of colleagues. At this time, we are pleased to provide you with this
Oncology supplement. It contains several reports that highlight much
of the information that was presented at our conference.
1. van Zandwijk N, Crino L, Kramer GW, et al: Phase II study of
gemcitabine plus cisplatin as induction regimen for patients with
stage IIIA nonsmall-cell lung cancer by the EORTC Lung Cancer
Cooperative Group (EORTC 08955) (abstract). Proc Am Soc Clin Oncol
2. Vokes EE, Leopold KA, Herndon JE, et al: A randomized phase II
study of gemcitabine or paclitaxel or vinorelbine with cisplatin as
induction chemotherapy and concomitant chemoradiotherapy for
unresectable stage III nonsmall-cell lung cancer (CALGB study
9431) (abstract). Proc Am Soc Clin Oncol 18(1771):459a, 1999.