Gallium scans in the management of patients with Hodgkin's disease: a study of 101 patients.

PURPOSE: To evaluate the utility of periodic gallium (67Ga) scans in the management of patients with Hodgkin's disease. PATIENTS AND METHODS: From 1990 to 1994, 101 patients treated for Hodgkin's disease (stage I to II, n = 67; stage III to IV, n = 34) had a positive 67Ga scan at the time of diagnosis. Treatment included chemotherapy in 27 patients, radiation therapy in 28, and combined modality therapy in 46. All patients underwent 67Ga scans at the time of diagnosis, near the end or just after treatment, and at periodic follow-up evaluation. RESULTS: After treatment, the 67Ga scan remained positive in four patients and was interpreted as negative in 97. Among the four patients with positive scans, two died of progressive disease and two relapsed. Among the remaining 97 patients with negative 67Ga scans, 16 patients relapsed, including five with stage I to II (7.5%) and 11 with stage III to IV (34.4%) disease. The negative predictive value of posttherapy 67Ga scan was 83.5% for all patients; however, when calculated according to stage, it was 92.4% for patients with stage I to II disease and 64.5% for patients with stage III to IV disease (P < .01). CONCLUSION: A positive 67Ga scan at the end of therapy is rarely seen in patients with Hodgkin's disease and should be considered a manifestation of gross residual disease. However, a negative 67Ga scan after therapy had a significantly lower predictive value in patients with stage III to IV disease compared with stage I to II disease. The predictive value of 67Ga scans, as well as newer imaging studies, should be analyzed according to pretreatment stage.

Future challenges in the clinical development of thymidylate synthase inhibitor compounds.

Thymidylate synthase (TS) is a folate-dependent enzyme that plays a critical role in providing the thymidylate nucleotide precursors essential for DNA biosynthesis. Given the increased metabolic demands that accompany malignant cell proliferation, it has been well-appreciated that TS represents an important target for cancer therapy. The fluoropyrimidines were the first class of agents to be directed against TS. As a result of extensive preclinical and clinical investigations, new inhibitor compounds of TS were subsequently designed and developed. This class of antifolate analogues includes ZD1694 (Tomudex), LY231514 (MTA), BW1843U89, ZD9331, AG331, and AG337. Although each of these analogues acts to inhibit TS, the data from both preclinical and early clinical studies suggest that they may each have a different spectrum of tumors against which they are active. In this commentary, an update of the current status of TS inhibitor compounds is presented. Finally, the future challenges that lie ahead in the clinical development with specific focus on identifying those critical factors that will determine the spectrum of antitumor activity and therapeutic selectivity of this interesting class of compounds are discussed.