FP Therapy Research Articles

左下肢の発赤と腫脹を主訴に来院した進行期乳房外Ｐａｇｅｔ癌の１例

A 78-year-old female visited our hospital, representing a swollen left leg with erythema. Physical examination revealed an 8×5××2cm in diameter on the left labia majus and minus pudendi, and a 3×2×1cm in diameter on the right labium minus pudendi. The histological findings of a biopsy specimen from these tumors showed a mass of Paget cells with deep dermal invasion. These were positive for immunohistochemical staining PAS, anti-CEA and CK7, but negative for CK20. Furthermore, the erythema lesion from the left leg revealed the lymph duct's ectasis containing the mass of aggregated Paget cells. The clinical appearance and histochemical findings of reddish and swollen lesions seen in this patient might be one of the characteristics of metastasis and infiltration of Paget's cells to the lymph duct. We diagnosed the condition as extramammary Paget's carcinoma (T4N2M1).We tried operation and low dose FP therapy. The redness and swelling in the leg was gradually decreased by the low dose FP therapy. The patient died about 5 months after visiting our hospital, but we conclude that the low dose FP therapy is worth trying against the inflammation of metastatic Paget's carcinoma of the lymph duct. [Skin Cancer (Japan) 2002; 17: 234-237]

Conceptual changes in cancer chemotherapy: from an oral fluoropyrimidine prodrug, UFT, to a novel oral fluoropyrimidine prodrug, S-1, and low-dose FP therapy in Japan.

The conventional concept in cancer chemotherapy considers that no efficacy can be attained without provoking adverse reactions. We presented concrete descriptions based on a novel concept allowing us to emerge from the old one. Relief of adverse reactions, e.g., diarrhea, stomatitis, anorexia, and H&F syndrome, not only improves QOL of the patient but also allows prolongation of the treatment period without lowering patient compliance. We describe in this paper a therapeutic modality which is based on SRC (self-rescuing concept) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. Furthermore, we refer to combination therapy with 5-FU (CIV) and low-dose consecutive CDDP in which CDDP was used as a modulator of 5-FU and to the theory and practice of combination therapy with 5-FU (CVI) intermittent (Monday, Wednesday, and Friday) administration and low-dose CDDP consecutive administration in which a difference in cell cycle between gastrointestinal mucosal cell and tumor cell or between bone marrow cell and tumor cell was utilized. We intend in future to combine the abovementioned therapeutic modalities provoking less adverse reactions and being gentle to patients with cancer in an effort to further increase their life expectancy.

RECURRENT GASTRIC CARCINOMA (ENDOCRINE CELL TYPE) SUCCESSFULLY TREATED WITH COMBINATION CHEMOTHERAPY-A CASE REPORT-

A case of recurrent gfastric carcinoma (endocrine cell type) successfully treated with combination chemotherapy with divided low-dose FP therapy is reported. The patient was a 47-year-old man who underwent total gastrectomy and combined distal pancreatectomy and splenectomy in June 1995 after receiving a diagnosis of Borrmann type 2 gastric carcinoma. The overall degree of advancement was as follows: H0, P0, se, n2, and stage IIIb. The histologic diagnosis was endocrine cell carcinoma. The patient initially presented with loss of appetite and a palpable abdominal mass 18 months later. Abdominal computed tomography showed metastatic lesions in both lobes of the liver, a metastatic abdominal wall mass 3cm in diameter and located directly below the umbilicus, and a pelvic mass 4cm in diameter. The patient underwent divided low-dose FP therapy, and by the 10th course, the hepatic metastases showed complete responses, and the abdominal wall and pelvic masses showed partial responses. The patient was still in good health 2 year and 6 months after initiation of therapy. These results suggest that combination chemotherapy with divided low-dose FP therapy may be useful for the treatment of highly proliferative cancers such as endocrine cell carcinoma, which exhibits a highmalignant potential, and should be actively employed in the treatment of such cancers.

A CASE OF UNRESECTABLE PANCREAS CANCER TREATED WITH LOW DOSE CISPLATIN AND 5-FLUOROURACIL REGIMEN FOLLOWED BY A LONG SURVIVAL

This parer presents a case of pancretic cancer with liver and para-aortic lymph nodes involvement which was unresectable for prominent lymph nods metastasis and well responded to chemotherapy with low dose cisplatin and 5-fluorouracil. This patient was a 49-year-old man. After the unresectable operation, he was treated with chemotherapy of low dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with low dose FP therapy which was given weelky by i. v. drip infusion at the first day. The combination of intravenous infusion of 5-FU (250mg/body) and CDDP (20mg/body) adminintered weekly. At 10 weeks, the serum CA19-9 and DUPANII level decreased within normal limits and the metastatic liver tumor and pancreatic cancer disappeared. The patient was discharged from the hospital and was given the low dose FP therapy biweekly on outpatient setting. Urticaria which is side effect of CDDP appeared after 38 courses of the low dose FP therapy, and thereafter only 5-FU (150mg/day oral) was given. After that, the tumor stopped to grow. The patient has been doing well as of 5 years after the admission. The lom dose FP therapy for patients with unresectable pancreatic cancer is recommended for selected cases.

Complete regression of recurrent esophageal carcinoma with reduced expression of glutathione S-transferase-π by treatment with continuous infusion of 5-fluorouracil and low-dose cisplatin infusion

The mortality rate of recurrent esophageal carcinoma remains high because of its resistance to chemotherapy and radiation therapy. We present a patient with recurrent esophageal carcinoma, which dramatically disappeared after treatment with the combination of continuous infusion of 5-fluorouracil and low-dose cis-Diamminedichloroplatinum-II (cisplatin) infusion (FP therapy). Furthermore, we immunohistologically found that glutathione S-transferases (GST)-π, a marker of resistance to cisplatin, was faintly expressed both in the endoscopical biopsy specimens of recurrent tumor and in the resected specimens of esophageal carcinoma and metastatic lymph nodes. FP therapy was suggested to be effective for recurrent esophageal carcinoma. Immunostaining for GST-π might be a prospective marker for the sensitivity of esophageal carcinoma to FP therapy, particularly cisplatin.

Continuous infusion of 5‐fluorouracil and low dose cisplatin infusion for the treatment of advanced and recurrent gastric adenocarcinoma

BACKGROUND Several chemotherapy studies have suggested that continuous infusion of 5-fluorouracil (5-FU) is more effective than bolus 5-FU. In addition, 5-FU and cis-Diamminedichloroplatinum-II (cisplatin) in combination have been shown to have synergistic cytotoxicity against several human neoplasms. In this study, the authors evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion (FP therapy) in the treatment of advanced and recurrent gastric adenocarcinoma. The relationship between the response to FP therapy and several factors was also examined. METHODS A total of 26 patients fulfilling standard eligibility criteria were enrolled in the trial. FP therapy consisted of 5-FU (350 mg/m2/day every day by continuous infusion) and cisplatin (7.5 mg/m2/day in 100 mL of normal saline infused over 1 hour on Days 1-5 every week) for 4 weeks. RESULTS A complete response was observed in 2 cases and a partial response in 11 cases, for an overall response rate of 50%. Patients with good performance status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferentiated histologic type (28.6% and 35.3%, respectively), although there were no significant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption. CONCLUSIONS FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity. Cancer 1997; 80:1-7. © 1997 American Cancer Society.

Continuous infusion of 5‐fluorouracil and low dose cisplatin infusion for the treatment of advanced and recurrent gastric adenocarcinoma

Several chemotherapy studies have suggested that continuous infusion of 5-fluorouracil (5-FU) is more effective than bolus 5-FU. In addition, 5-FU and cis-Diamminedichloroplatinum-II (cisplatin) in combination have been shown to have synergistic cytotoxicity against several human neoplasms. In this study, the authors evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion (FP therapy) in the treatment of advanced and recurrent gastric adenocarcinoma. The relationship between the response to FP therapy and several factors was also examined. A total of 26 patients fulfilling standard eligibility criteria were enrolled in the trial. FP therapy consisted of 5-FU (350 mg/m2/day every day by continuous infusion) and cisplatin (7.5 mg/m2/day in 100 mL of normal saline infused over 1 hour on Days 1-5 every week) for 4 weeks. A complete response was observed in 2 cases and a partial response in 11 cases, for an overall response rate of 50%. Patients with good performance status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferentiated histologic type (28.6% and 35.3%, respectively), although there were no significant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption. FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity.