Aggressive Treatment More Effective for Nasopharyngeal Cancer

Radiation therapy (RT) has been the most important treatment modality with curative potential in treating patients with cancer of the nasopharynx, the part of the pharynx that lies above the soft palate. This is due to several factors: (1) undifferentiated carcinoma, or tumour cells with no resemblance at all to normal glandular or surface lining cells, is quite radiosensitive and is more common than squamous cell carcinoma; (2) more than two-thirds of the patients present with cervical lymph node metastases at time of diagnosis; (3) about half of the patients present with bilateral cervical metastases; (4) retropharyngeal lymph node, which is difficult to remove surgically, is frequently involved at rather earlier stages.

Local control and survival rates have been improved by increasing the radiation dose since 1950’s, and favorable 10-year survival rates ranging from 65 to 77 percent were achievable in patients with early stage disease by high dose radiation therapy. However, the long-term survival rates in those with high T or N stages are not satisfactory because of either poor local control or frequent distant metastases. The addition of systemic chemotherapy to high dose RT has been widely tried in an effort to overcome these limitations.

Three sequences of combining chemotherapy RT have been tried: chemotherapy before surgery followed by radiation therapy; adjuvant chemotherapy after RT; and concurrent radiochemotherapy. Based on several phase III trials, positive role of chemotherapy that was added to RT in locally advanced nasopharynx cancer was proved, and the concurrent fashion was regarded, if not conclusive, as the most effective strategy.

High dose radiation therapy with concurrent systemic chemotherapy in the patients with locally advanced nasopharynx cancer has been the treatment policy at a South Korean medical institute since 1995. Staff members at the institute set out to analyze and report the failure patterns and survival outcomes associated with this treatment. Their findings can be found in the research effort, “High Dose Radiation Therapy Concurrent with Chemotherapy in Locally Advanced Nasopharynx Cancer,” authored by Min Kyu Kang, MD, Yong Chan Ahn, MD, Won Park, MD, Keunchil Park, MD, Chung-Hwan Baek, MD, Young Ik Son, MD, Jeong Eun Lee, MD, Young Je Park, MD, Hee Rim Nam, MD, Kyoung Ju Kim, MD, Do Hoon Lim, MD, and Seung Jae Huh, MD, all from the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Their findings are to be presented at the 6th International Conference on Head and Neck Cancer being held August 7-11, 2004, at the Wardman Park Marriott, in Washington, D.C.

Methodology: Sixty patients with nasopharynx cancer received high dose curative radiation therapy at the authors’ institute from April, 1995, to May 2001. Excluding eight patients who received high dose RT alone, 52 were given high dose radiation therapy with concurrent systemic chemotherapy. To be eligible for this treatment protocol, patients needed to (1) have locally advanced stage disease, (2) be in ECOG performance score from 0 to 2, (3) have no major medical illness that would hinder this rather aggressive approach, (4) have adequate hematopoietic, hepatic, and renal reserves, (5) have no past history of malignancy other the current diagnosis, and (6) consent to this protocol.

The treatment consisted of:

Radiation therapy: RT was administered using 4 MV or 6 MV x-rays generated from a linear accelerator. Conventional fractionation schedule to deliver five daily fraction of 1.8 Gy per week was used. Serial shrinking field technique was applied to all patients, and the median doses to the primary lesions and grossly enlarged lymph nodes, were 72 (64~80) Gy and 59.4 (37.8~72) Gy. The elective lymphatic irradiation volume and its radiation dose were individually determined based on the initial clinical findings, and the median elective lymphatic irradiation dose was 45 (36~45) Gy.

Chemotherapy: Two types of chemotherapy regimen and schedule were used. Eight patients received Regimen A: two cycles of concurrent FP chemotherapy (5-fluorodeoxyuridine 1,000 mg/m2/day, continuous intravenous infusion for four days + cisplatin 75 mg/m2, intravenous infusion on day 1) at four weeks’ interval plus four cycles of adjuvant chemotherapy with the same doses schedule following radiation therapy. Regimen B included: three cycles of concurrent CDDP single agent chemotherapy (cisplatin 100 mg/m2, intravenous infusion on day 1) at three weeks’ interval plus three cycles of adjuvant FP chemotherapy (5-fluorodeoxyuridine 800 mg/m2/day, continuous intravenous infusion for five days + cisplatin 75 mg/m2, intravenous infusion on day 1) at three weeks’ interval following RT. Regimen B was used in 44 patients who were enrolled during the later study period since July, 1996.

All the patients were examined by fiberoptic nasopharyngoscopy on weekly-basis during the RT course. The response was evaluated based by CT or MR images taken within one month of radiotherapy completion. Following completion of the planned treatment schedule including adjuvant chemotherapy, CT, or MR images were repeated every three to four months for the first two years, and every four to six months thereafter.

Results: This study was unique in that the radiation therapy boost technique used for most of the patients in the study was characterized by three-dimensional conformal techniques, while other high dose radiation therapy trials used conventional two-dimensional ways. Resulting side effects by radiation therapy were much lower in incidence and milder in severity. As for chemotherapy regimen, eight patients received FP regimen with poor compliance. However, after changing into a single agent (CDDP) regimen for 44 patients during their radiation therapy, providing a radiosensitizing effect rather than curative cancericidal effect, compliance became much better.

Conclusions: This difference based on the chemotherapy regimen has been first proved in this study, even though this study was not conducted in a prospective randomized fashion. These factors enabled the researchers to achieve high local control rate and survival compared with other trials of concurrent radiochemotherapy.