s-1-(combination) and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib.. A 70-year-old man had undergone surgery three times for sigmoid colon cancer and recurrence. Systemic chemotherapy with S-1 plus oxaliplatin plus bevacizumab as a clinical trial had already been administered because of metastatic colon cancer. The patient's medical history was CML, and he had been receiving dasatinib treatment (100 mg once daily). Based on the diagnosis of unresectable and multiple metastases, S-1 monotherapy was started. S-1 (120 mg/day) was taken for 28 consecutive days, followed by a 14-day rest. Blood samples were obtained before and after the first administration of S-1. The plasma pharmacokinetics of S-1 were comparable to a pharmacokinetics study of S-1.. The area under the plasma concentration-time curve (AUC0-8) of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), oxonate (Oxo), and 5-fluorouracil (5-FU) was 4,309.2, 716.3, 86.8, and 492.75 ng h/mL, respectively, after S-1 administration. The pharmacokinetics of FT, CDHP, Oxo, and 5-FU after treatment with S-1 were not significantly different from a phase I pharmacokinetics study of S-1. During treatment with S-1 and dasatinib, CML relapse and serious myelosuppression were not observed.. Our report suggests that S-1 is an important treatment option for recurrent colorectal cancer in patients with CML treated with dasatinib.

Topics: Aged; Antimetabolites, Antineoplastic; Area Under Curve; Colonic Neoplasms; Dasatinib; Drug Combinations; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Protein Kinase Inhibitors; Pyrimidines; Tegafur; Thiazoles

A 78-year-old man received total gastrectomy for advanced gastric cancer in September 2006, and was subsequently treated with oral anti-metabolite TS-1 for 38 months. He had no evidence of recurrence of gastric cancer, although he had a continuous poor appetite due to TS-1. Leukocytosis was found in November 2008. On the basis of bone marrow findings, Philadelphia chromosome and BCR-ABL fusion gene, he was diagnosed as having chronic phase of secondary chronic myeloid leukemia (CML). Two weeks after starting imatinib therapy, skin eruption, palpebral edema and appetite loss were observed; moreover, thrombocytopenia gradually worsened. He stopped taking imatinib and hydroxyurea was subsequently started. The above symptoms disappeared and the platelet count normalized. CML is rare in secondary leukemia. Our case is the second reported case of secondary CML following TS-1 treatment and suggests that therapy for secondary CML should be selected on the basis of QOL in patients with advanced cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Benzamides; Drug Combinations; Fatal Outcome; Gastrectomy; Humans; Hydroxyurea; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neoplasms, Second Primary; Oxonic Acid; Piperazines; Pyrimidines; Stomach Neoplasms; Tegafur

A 55-year-old woman had received total gastrectomy for advanced gastric cancer in March 2002, and was subsequently treated with adjuvant chemotherapy using oral anti-metabolite TS-1 for 21 months. She was well with no evidence of recurrence of gastric cancer, but leukocytosis was found in June 2005. The analysis of bone marrow revealed that Philadelphia (Ph) chromosome and bcr-abl fusion gene were positive. On the basis of these findings, the chronic phase of secondary chronic myeloid leukemia (CML) was diagnosed. Three months after being started on imatinib therapy, Ph chromosome positive cells disappeared in the bone marrow, and a complete cytogenetic response was achieved. Although CML is rare in secondary leukemia, this is, to our knowledge, the first reported case of therapy-related CML following TS-1 treatment. The present case suggested that imatinib therapy was also effective for secondary CML as well as de novo CML.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Benzamides; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Fusion Proteins, bcr-abl; Gastrectomy; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Neoplasms, Second Primary; Oxonic Acid; Piperazines; Pyrimidines; Stomach Neoplasms; Tegafur