Gemcitabine Activity in Nasopoharyngeal Carcinoma

Abstract & commentary

Synopsis: Type 2 nasopharyngeal carcinoma occurs most commonly in the Far East. However, patients with this tumor are being increasingly treated in North America with the increase in the number of Asian communities, particularly in urban areas. In this trial, patients with recurrent, locally advanced, or metastatic nasopharyngeal cancer who presented to a single institution for a 22-month period were treated with either gemcitabine alone or in combination with cisplatin. The experience indicates that these drugs can safely offer effective palliation. However, the experience presented should be considered exploratory, and larger, randomized studies are still needed to determine the most effective agents, combinations, and clinical circumstances in which such patients should be treated with chemotherapy.

Source: Ma BB, et al. Cancer. 2002;95:2516-2523.

Nasopharyngeal cancer (NPC) is common in Asia, and clinical trials there have indicated that gemcitabine, either alone or in combination with cisplatin, has antitumor activity. North American oncologists are also confronted with increasing numbers of patients with NPC, especially among the increasing numbers of Asian immigrants. In the current report, Ma and colleagues at the Princess Margaret Hospital detail their experience with gemcitabine with or without cisplatin, in patients with NPC. For an approximate 2-year period, 32 patients with NPC were treated with gemcitabine (n = 18) or gemcitabine with cisplatin (n = 14). Patients either received 1000 mg/m2 gemcitabine (GEM) on days 1, 8, and 15 every 28 days as a single agent, or with cisplatin (GC) given on day 2, at 70 mg/m2.

Most of the patients (91%) were of Southeast Asian ancestry, and the great majority (91%) had type 2 (World Health Organization 1991 classification) non- keratinizing histology.1 At the initiation of treatment, 61% of the patients treated with GEM alone and 43% in the GC group had distant metastases. Performance status was also lower for patients receiving GEM alone and prior chemotherapy experience was greater. Before being offered either GEM or GC, patients with local disease recurrence were assessed for eligibility for salvage surgery (radical neck dissection), re-irradiation, or brachytherapy. Thus, included patients were those not eligible to receive further local therapy due to significant risks of damage to normal tissues.

Patients in both groups (GEM and GC) received a median of 4 cycles of chemotherapy. Reduction of the dose of GEM occurred in 17 of 75 cycles (23%) and 18 of 67 cycles (27%) of GC, and the majority of these were due to myelosuppression on day 15, necessitating dose reduction or delays. However, such delays beyond 7 days were reported as "infrequent."

This was not a randomized trial and the GEM group was mostly pretreated (89% had prior chemotherapy). Partial responses were observed in 5 (28%) and 1 patient had a complete response. In the GC group, there were 2 CRs (14%) and 7 PRs (50%), giving an overall response rate of 64%. The median duration of response for the GEM and GC patines was 17 and 24 weeks, and the 1-year survival rate was 48% and 69% respectively. Thus, this report confirms that GEM is an active and tolerable drug for patients with NPC.

Comment by William B. Ershler, MD

North American ENT surgeons and oncologists, particularly those in urban areas, are treating an increased number of nasopharyngeal carcinomas, due in a major way, to the increased numbers of first- and second-generation Asian emigrants.2 Nasopharyngeal carcinoma had been uncommon in North America, but is endemic in Southeast Asia, North Africa, and the Mediterranean. In these endemic areas, the carcinomas are typically non keratinizing or undifferentiated and are associated with Epstein Barr virus infection. Second-generation, North American-born Chinese emigrants also have a high incidence of this malignancy, estimated to be 6 times greater than Caucasians.3

The main objective of this study was to document the tumor response and toxicity of gemcitabine, with or without cisplatin in patients with nasopharyngeal carcinoma. Previously, reports out of Asia demonstrated the potential use of gemcitabine in patients with recurrent or refractory nasopharyngeal cancer.4 This report, from the Princess Margaret Hospital in Toronto, affirms this activity and substantiates the role of gemcitabine for palliative treatment of nasopharyngeal carcinoma. Furthermore, the experience indicates that the gemcitabine-cisplatin combination was well tolerated and also effective. However, because the 2 groups were not randomized or comparable with regard to stage of disease and patient performance status, it is impossible to tell from the data presented whether the combination is more effective than either agent alone. Nonetheless, extrapolating from experience with other tumor types, including non-small-cell lung cancer and transitional-cell bladder cancer, the combination is likely to be superior to either single agent alone, and with nonoverlapping toxicities, the 2 drugs can be administered safely.

It should be recalled that the synergism witnessed for gemcitabine and cisplatin is schedule dependent, as the experience with non-small-cell lung cancer has indicated that cisplatin administered on day 2 (at doses of 70 or 100 mg/m2) was superior to when given on day 1, without affecting hematological toxicity.5 Therefore, this combination and schedule is a reasonable approach for patients with locally advanced, recurrent or metastatic nasopharyngeal carcinoma. However, before such becomes the standard of care, additional, larger-scale studies are needed. Furthermore, because there were so few patients in the current trial with type 1, keratinizing or differentiated NPC, the application of these findings to patients (more typically Caucasian) would be inappropriate.

References

1. World Health Organization. International classification of tumors: Histological typing of upper respiratory tract tumors. Geneva, 1991.

2. Sutton JB, et al. Am J Clin Oncol. 1995;18:337-342.

3. Wang ZJ, et al. Int J Epidemiol. 1989;18:17-21.

4. Leong SS, et al. Ann Oncol. 2002;13:150-156.

5. Shepard FA, et al. Lung Cancer. 2000;30:117-125.