A case of breast cancer with liver metastases responding remarkably to combination therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA)]

A 60-year-old woman with her right breast cancer showing simultaneous and multiple liver metastases was initially treated with CEFT [cyclophosphamide (CPA), epirubicin (epi-ADM), 5-fluorouracil (5-FU), tamoxifen (TAM)]. After one treatment course the primary lesion did not decrease while tumor markers and liver lesion size increased. Therefore, the foul-smelling primary lesion was resected followed by treatment with mitoxantrone (MIT), 10 mg intravenously every 4 weeks as well as daily/oral administrations of doxifluridine (5'-DFUR) and medroxyprogester-one acetate (MPA). Following MIT administration, the tumor markers decreased markedly, so treatment was continued. After the third course, therapy was continued on an outpatient basis. During treatment WBC reduction to about 3,000/microliter was the only adverse reaction. After 10 courses, the tumor markers were normal, and after 15 courses there were no liver metastases on abdominal CT. Generally, patients with resistance to standard anthracycline chemotherapy are difficult to treat. Those with liver metastasis especially have a poor response which results in a poor prognosis. However, therapy with MIT, 5'-DFUR and MPA may be useful in previously treated, advanced and recurrent breast cancer. Furthermore, this therapy can be done on an outpatient basis, which presumably improves the quality of life (QOL).     

A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA), medroxyprogesterone acetate (MPA) and pamidronate disodium therapy

A 49-year-old female underwent bilateral breast preserving surgery for heterochronic breast cancers. She later developed a sternal metastasis and was recommended for intravenous chemotherapy. However, she refused such an intensive therapy and opted for immunotherapy. Afterward, she came to our hospital because of spinal metastases with back pain. She was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for 3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate disodium 30 mg intravenously every 4 weeks. This combined chemotherapy relieved her pain after one course. After 5 courses, tumor markers were reduced to the normal range. After 14 courses, bone X-P revealed that the osteolytic bone showed sclerotic changes and bone scintigraphy showed a complete remission (CR). The adverse effects were not remarkable. This regimen is possible on an outpatient basis, and it may play an important role from the standpoint of treatment effectiveness and the quality of life of the patient.     

Successful treatment of disseminated breast cancer with combination therapy of 5'-deoxy-5'-fluorouridine (5'-DFUR), medroxyprogesterone acetate (MPA) and cyclophosphamide (CPA)]

A 54 year-old female patient with disseminated breast cancer refractory to various kinds of previous therapies was treated with a combination therapy of 5'-DFUR, MPA and CPA. Partial response (PR) was obtained both against pleural and liver metastases with complete disappearance (CR) of soft tissue lesions and was still being continued for the following 7 months. No serious side effects were observed except for a mild degree of diarrhea and moon face. The patient was enjoying a favorable quality of life. We confirmed that this combination regimen was effective as the second line treatment for disseminated breast cancer.     

The efficacy of combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), cyclophosphamide (CPA) and medroxyprogesterone acetate (MPA) for bone metastasis in breast cancer patients

5'-DFUR is a pro drug of 5-FU, which is known to be converted by thymidine phosphorylase (dThdPase). A recent pre-clinical study revealed that CPA upregulates dThdPase activity specifically in tumor cells. Furthermore, clinical trials have shown significant response rates in breast cancer patients, when using the chemotherapy combination of 5'-DFUR, CPA and MPA. The purpose of this study was to examine the efficacy of this regimen as a pain reduction therapy for breast cancer patients with bone metastasis. Ten patients who had bone metastasis with restricted ADL were included in the study. All of the patients had had previous exposure to such standard chemotherapy as CAF, CMF, taxol and oral 5-FU administration. The patients were administered daily oral doses of 5'-DFUR at 800-1,200 mg, CPA at 200 mg and MPA at 400-800 mg for two weeks as induction therapy, followed by two weeks rest (one to two cycles). Daily dose of 800 mg of 5'-DFUR, 100 mg of CPA, 400-800 mg of MPA was continuously administered thereafter. The main findings included a significant decrease in pain in eight patients, which continued for more than 6 months. In five patients, the effect lasted more than one year. As the pain decreased, the patients' QOL was improved. Hematological toxicity of more than grade 3 was observed in three patients but only during the induction therapy. One patient had pulmonary thrombosis and required hospitalization. In conclusion, oral administration of 5'-DFUR/CPA/MPA is well tolerated and useful in reducing pain.     

A case of recurrent breast cancer with multiple liver metastases responding to combination therapy of capecitabine and MPA

The patient was a 68-year-old woman who underwent left partial mastectomy on February 1999. The stage was T2N1. There were positive for estrogen and progesterone receptors in the tumor. After operation, adjuvant therapy consisting of oral administration of tamoxifen and radiation was performed. On February 2005, she felt dyspnea and right femoral pain. After examinations, she was diagnosed as recurrent breast cancer with pleuritis carcinomatosa and bone metastasis. The patient was treated with oral administration of anastrozole and pamidronate disodium 90 mg intravenously every 4 weeks, radiation of her right femur, and OK-432 injection into the intrapleural cavity. On November 2005, she felt general fatigue and anorexia. CT examination revealed multiple liver metastases. She was treated with oral combination chemoendocrine therapy with capecitabine (2,400 mg/day) and MPA (600 mg/day). After the four courses, multiple liver metastases were remarkably reduced in the CT findings. After twelve courses, the partial response continued. No adverse reactions occurred except for gain in weight of grade 1. It is suggested that this oral combination chemoendocrine therapy may be useful for recurrent breast cancer with consideration for treatment effectiveness and the quality of life of the patient.     

A case of postoperative recurrent breast cancer with multiple lung metastases that completely responded to combination therapy of docetaxel (TXT) and medroxyprogesterone acetate (MPA)

A 54-year-old female had undergone surgery for breast cancer 5 years ago, after which she developed multiple lung metastases, in spite of treatment with various postoperative chemoendocrine therapies. The patient who had recurrent breast cancer with multiple lung metastases was treated with a combination of docetaxel (TXT) 80 mg/body three cycles, two courses of 40 mg/body four times and medroxyprogesterone acetate (MPA) 600 mg p.o. daily. Six months later, the lung metastases had completely disappeared on chest CT-scan. Complete remission has been maintained for one and half years. The use of combined chemoendocrine therapy with TXT and MPA is considered effective for recurrent breast cancer as second-line therapy.     

A case of anthracycline and taxane-resistant breast cancer with life-thereatening multiple liver metastases responding to oral combination chemotherapy by UFT, cyclophosphamide and medroxyprogesterone acetate

A 53-year-old woman presented with an advanced right breast cancer together with skin manifestations and massive axillary lymph node metastases, as well as distant metastases in the lung and the liver. The patient received surgery after 6 courses of chemotherapy with epirubicine and intravenous cyclophosphamide (80/600 mg/m2). A weekly paclitaxel regimen (80 mg/m2) was started because the tumor markers increased soon after surgery. Despite chemotherapy, no response was confirmed, then weekly docetaxel (35 mg/m2) was started. Although the tumor markers decreased after administration of docetaxel, severe liver disfunction appeared and did not improve after cessation of docetaxel. Computed tomography (CT) revealed numerous metastatic nodules in the bilateral lobes of the liver. UFT (400 mg/day) and cyclophosphamide (100 mg/day) were administered for 4 weeks followed by 2 weeks cessation and then combined with continuous medroxyprogesterone acetate (800 mg/day). Liver function tests were normalized 3 months after, and the massive metastatic liver tumors disappeared completely. Lung metastasis also subsided. In spite of these good responses, tumor markers did not normalize and skin nodules appeared around the surgical site. Administration was stopped 36 weeks after initiation of the treatment.     

Advanced breast cancer with multiple bone metastases successfully treated with combined chemoendocrine-therapy of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) and 5'-DFUR (5'-deoxy-5-fluorouridine) + MPA (medroxyprogesterone acetate)--a case report

We report the case of a 51-year-old female with stage IV advanced breast cancer accompanied by multiple bone metastases. A hard mass of about 3.0 cm in diameter was palpated just below the nipple. An excisional biopsy was performed and histological examination revealed infiltrated solid tubular adenocarcinoma. There were no estrogen or progesterone receptors in the tumor. Modified radical mastectomy was performed in October, 1998. Postoperative adjuvant therapy with 10 cycles of CEF therapy was undertaken for one year. Combined chemoendocrine therapy with 5'-DFUR and MPA was also conducted for 11 months. Bone scintigraphy showed that all bone metastatic lesions disappeared completely one year after the operation. Mild bone marrow suppression, alopecia and body weight gain were observed as side effects. It is suggested that this combination therapy may be useful for advanced breast cancer patients with multiple bone metastases.     

A case of long surviving advanced recurrent breast cancer with multiple bone metastases responding to treatment with 5'-DFUR combined with MPA

The patient was a 69-year-old woman who had undergone right standard radical mastectomy on August 8, 1991, and was treated with chemo- and hormonal therapy of ADM, UFT and TMA. Three years later she showed multiple bone metastases with elevation of CEA, and 5'-DFUR 1,200 mg/day and MPA 800 mg/day were administered. Two years later her CEA levels were decreased, 5'-DFUR was discontinued and MPA 1,200 mg/day only was continued. Two months later a side effect of MPA, her body weight gain, was observed, and the dosage of MPA was reduced from 1,200 mg/day to 800 mg/day. Then the side effect was resolved. Bone scintigraphy and MRI showed that bone metastatic lesions were reduced 6 years after 5'-DFUR and MPA therapy. It is suggested that this combination therapy may be useful for advanced recurrent breast cancer patients with multiple bone metastases.     

Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.     

A case of gastric cancer with multiple liver metastases responding to combination therapy of recombinant interferon-gamma (KW-2202) and 5-FU

A 65-year-old man with gastric cancer showing multiple liver metastases was treated with recombinant interferon-gamma (KW-2202) and 5-fluorouracil (5-FU). Three months after this combination therapy, the metastatic liver masses showed remarkable reduction in both number and size. Also, the primary gastric tumor showed a definite size reduction. Judging from these findings, subtotal gastrectomy and resection of the metastatic liver mass were performed. This case of gastric cancer with multiple liver metastases was thus shown to well to combination therapy with KW-2202 and 5-FU.     

A case of liver metastasis of colon cancer responding remarkably to 5'-DFUR

A 65-year-old man was referred to our hospital because of diarrhea due to sigmoid colon cancer. Abdominal CT scan revealed a hepatic tumor (S8) about 2 cm in diameter. We performed a sigmoidectomy and planned to resect the liver metastasis 1 or 2 months later. Pathological findings showed moderately differentiated adenocarcinoma, s, n1. Two weeks after the surgery, 5'-DFUR was administered at 600 mg/day. An abdominal CT scan 2 months later demonstrated regression of the liver metastasis and another scan 4 months later showed the tumor had disappeared. 5'-DFUR was administered for about 2 years. Five years after the surgery, the patient is alive without recurrence and CEA level is in normal range.     

A comparative study with 5'-DFUR alone or in combination with tamoxifen (TAM) or medroxyprogesterone acetate (MPA) for advanced or recurrent breast cancer]

A comparative study of 5'-DFUR 600 mg/day alone (C-arm) or in combination with TAM 30 mg/day (A-arm) or MPA 600 mg/day (B-arm) was carried out. Thirty-four patients (aged 80 or less) with no prior treatment were evaluable, and the following results were obtained. 1) Patient characteristics were similar in each treatment group and the compliance in all groups was excellent. 2) The group B response rate (70.0%) was considerably higher than that of group A (23.1%) and C (27.3%). 3) In B, the response rates in soft tissues (80.0%) and bone (71.4%) were still good. 4) Mild side effects were encountered in about 15% of each group. We confirmed that combination chemotherapy with a low dose of 5'-DFUR and MPA was effective for first line treatment of metastatic breast cancer.     

Two cases of advanced breast cancer responding to oral chemoendocrine therapy with 5'-deoxy-5-fluorouridine, medroxyprogesterone acetate and cyclophosphamide (DMpC)

Two patients were diagnosed as advanced breast cancer with multiple bone metastases. DMpC therapy (oral chemoendocrine combination therapy with doxifluridine, medroxyprogesterone acetate and cyclophosphamide) was chosen as first-line chemotherapy. After one month of the treatment, reductions in the primary tumors, lymph node metastases and metastatic bone lesions were noted. Only grade 2 leukopenia was observed as an adverse event in only one patient. DMpC therapy is an effective, easy and safe oral therapy. Therefore, it is possible to continue medication on an ambulatory basis for the long-term. DMpC therapy could thus be one the most useful treatments for advanced breast cancer.     

Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients

BACKGROUND:: The Comprehensive Cancer Center trial 82-01 is a prospectiverandomized study to investigate the value of the addition ofhigh-dose medroxyprogesterone acetate (MPA) to chemotherapyin patients with node-positive operable breast cancer. MPA maybe of advantage in this setting because of its activity in estrogenreceptor ER-positive as well as ER-negative tumors and sinceit may protect against chemotherapy-induced myelosuppressionand thus enable maintenance of the appropriate chemotherapeuticscheduling PATIENTS AND METHODS:: Four hundred eight evaluable patients with node-positive (N+)operable breast cancer (Tl-3, Nl) were entered in a multicenterrandomized trial. Two hundred nine patients were randomizedin the MPA– arm and 199 in the MPA+ arm. CAF chemotherapywas given as a short i.v. bolus infusion: cyclophosphamide 500mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. day 1, and 5-fluorouracil500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly(i.m.) 500 mg q d / 28 days, followed by 500 mg i.m. twice weeklyduring 5 months. RESULTS:: The main side effects of MPA were weight gain with a mean of5.5 kg as opposed to 1.8 kg in the control group (p = 0.01)and vaginal bleeding in 30/199 in the MPA+ group and 0 in theMPA– group. MPA ameliorated vomiting grade III, IV (45%vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p< 0.001) and leucocyte nadir grade III, IV (20% vs. 11%,p – 0.003). Disease-free survival (DFS) after 5 yearswas 59% in the MPA+ and 49% in the MPA– group (p = 0.12).Patients >>60 years benefitted most from MPA treatment,in particular if freedom from distant metastases was taken asthe endpoint (p = 0.02). Overall survival (OS) was not significantlydifferent between the two treatment groups (p – 0.18),but within subgroups analysed there was an advantage for MPA+in patients > 55 years (p – 0.002) and in pTl patients(p – 0.045). CONCLUSIONS:: High-dose MPA ameliorates CAF side effects and reduces the riskof metastatic disease, especially in elderly breast cancer patients. adjuvant chemohormonal therapy, breast cancer, medroxyprogesterone acetate     

5-Fluorouracil, adriamycin and cyclophosphamide combined with high-dose medroxyprogesterone acetate in advanced breast cancer

Seventy-six patients with metastatic breast cancer were treated with fluorouracil, adriamycin (doxorubicin) and cyclophosphamide (FAC) plus high-dose medroxyprogesterone acetate (HD-MPA). MPA was given for 21 days at the dose of 500 mg/day i.m., then on a randomized basis, either 500 mg/week i.m. (FAC+HD-MPA i.m.) or 300 mg/day p.o. (FAC+HD-MPA p.o.). Objective response rates were 79% in 39 patients on FAC+HD-MPA i.m. and 73% in the 37 patients on FAC+HD-MPA p.o. There was no significant difference in the median duration of response and median survival for the 2 regimens (respectively, 17 months and 22 months, and 15 months and 21 months for FAC+HD-MPA i.m. and FAC+HD-MPA p.o.). Toxicity was mild and similar in both groups. Although FAC+HD-MPA was highly effective, at present it is difficult to select which regimen provides the best initial treatment for metastatic breast cancer.     

A case of advanced breast cancer responding to low-dose 5'-DFUR]

A 69-year-old female patient with locally advanced breast cancer with multiple bone metastases (T4cN2-M1) was treated with 5'-DFUR after failure of tamoxifen treatment. The 5'-DFUR dose was limited to 600 mg per day, half the usual dose, because of its gastroenterological side effects. The primary tumor and metastatic axillary lymph nodes regressed three months after the start of treatment, and the complete remission of lesions was obtained in 16 months. Reduction of bone metastasis was confirmed by the disappearance of osteolytic lesion in the skull roentgenogram and the decrease of abnormal accumulation on the bone scintigram. Serum levels of CEA and ST-439 markedly reduced during the treatment as the disease regressed.     

A case of inflammatory breast cancer treated with medroxyprogesterone acetate (MPA) in combination with intra-arterial infusion chemotherapy]

A 55-year-old female with severe inflammatory breast cancer was treated with the combined use of MPA and the intraarterial infusion chemotherapy. One cycle consisted of 4'-epi-adriamycin; 210 mg (day 1, 4 and 8) and daily administration of MPA; 1,200 mg. A marked shrinkage of the tumor was obtained with this treatment. The regressive change was noted not only in the primary lesion but in lymph nodes of the axillary region. Therefore, the combined use of MPA with intra-arterial infusion chemotherapy may well contribute to the treatment of inflammatory breast cancer.     

Doxifluridine, medroxyprogesterone acetate and cyclophosphamide(DMpC)combination therapy found effective for case of chest wall recurrent breast cancer with bone and pleural metastases

A 67-year-old woman in poor general condition consulted my clinic with complaints of dyspnea and right chest wall pain. There was a huge and moist ulcer, caused by recurrence and post-radiation, on her right anterior to posterior chest wall. A chest X-ray demonstrated massive pleural effusion. Bone scinti gram showed multiple metastases in the spine, femur and pelvis. Her general condition was so poor that standard chemotherapy was unsuitable. Therefore, the patient was orally administered DMpC(doxifluridine, medroxyprogesterone acetate and cyclophosphamide)combination therapy. The pleural effusion had completely disappeared after 11 weeks, and the elevated serum CA15-3 and CEA value returned to a normal range 13 weeks later. No side effects were observed from this therapy. The patient clinically achieved good QOL in 6 months form this therapy with zoredronic acid administration. DMpC therapy appears to have few side effects and might be an effective treatment option for recurrent breast cancer patients with a poor general health condition.     

A case of gastric carcinoma remarkably responding to etoposide, adriamycin and cisplatin (EAP) therapy

A 47-year-old male was diagnosed as having gastric cancer with metastases to liver, para-aorta node and Virchow node. He was treated with EAP (Etoposide, Adriamycin, Cisplatin) therapy, as a result of which a partial response was obtained according to the criteria of the Jpn. Soc. Cancer. Ther. The response was disappearance of subjective symptoms and Virchow's metastasis and reduction of chief tumor and liver metastases. However, this therapy was accompanied by severe side effects such as leucopenia and thrombocytopenia, but in this case, these side effects improved within 20 days.