Abstract
Background. A transient increase in the serum alkaline phosphatase (ALP) level is sometimes observed in cancer patients with bone metastases who are receiving cancer therapy. This change is called the "ALP flare phenomenon". We encountered the ALP flare phenomenon in two patients with lung carcinoma with bone metastases who showed dramatic improvements with gefitinib treatment. Case. Case 1 involved a 64-year-old female with a mutation in the epidermal growth factor receptor (EGFR) gene. On the 10th day of gefitinib therapy, the ALP level was increased 2-fold over the baseline level. Case 2 involved a 46-year-old male with a mutation in the EGFR gene. On the 18th day of gefitinib therapy, the ALP level was increased 2-fold over the baseline level. In both cases, a large peak was observed in the ALP 2 and ALP 3 levels composed of 90% of the ALP isozyme peak. We speculated that the ALP elevation was derived from the bone, because no increases in other liver enzyme levels were observed. After one month of therapy, bone scintigrams showed a marked increase in tracer uptake. Although this finding could be attributed to progression of the bone metastases, computed tomography scans demonstrated a reduction in the size of the other lesions, and the tumor marker levels also decreased. These observations indicated the occurrence of the ALP and bone scintigraphic flare phenomenon, and the gefitinib therapy was therefore continued. After five months of therapy, the patient in case 1 exhibited improved bone scintigraphic findings highlighted by reduced tracer uptake. Subsequently, the ALP levels decreased, and both patients responded to gefitinib therapy. Conclusions. When ALP elevation is observed in lung cancer patients with bone metastasis who are receiving gefitinib therapy, the ALP flare phenomenon should be differentiated from the progression of bone metastases or any adverse effects of gefitinib therapy by integrating all available clinical data.
