5'-deoxy-5-fluorouridine (5'-DFUR), mitomycin C (MMC), etoposide and medroxy progesterone acetate (MPA) in a previously treated patient with advanced breast cancer]

An advanced breast cancer patient refractory to CAF (Cyclophosphamide, Adriamycin, 5-fluorouracil), 5-FU-Methotrexate sequential therapy and Tamoxifen was treated with the combination 5' DFUR, MMC, Etoposide and MPA. Complete response was obtained both against liver and lymph node metastases from 7 months after the initial treatment. A mild bone marrow suppression and appetite loss were observed as the side effect. It is suggested that the combination therapy may be useful for previously treated patients with advanced breast cancer.     

A case of advanced breast cancer with multiple lung, bone and lymph node metastases successfully treated with 5'-DFUR alone

A 78-year-old female patient with locally advanced breast cancer, bleeding from a deep ulcer, and with multiple bone, lung and distant lymph node metastases was successfully treated with 5'-DFUR alone. She was at first treated with docetaxel + 5'-deoxy-5-fluorouridine (5'-DFUR) + tamoxifen, but they were discontinued because of deep venous thrombosis. She underwent simple mastectomy due to periodically recurring bleeding and infection. After administration of 5'-DFUR alone, a decrease of abnormal accumulation on a bone scintigram was obtained in 10 months, the lung metastases were diagnosed as being in complete remission (CR) at 11 months and the lymph node metastases were diagnosed as being in CR at 14 months. These states have continued to the present. The administration of 5'-DFUR alone is suitable for tumor dormancy in some cases.     

A case of recurrent gastric cancer that responded dramatically to docetaxel and 5'-DFUR combination chemotherapy

A 54-year-old man suffering from Borrmann type 4 advanced gastric cancer with pancreatic invasion and paraaortic lymph node metastases underwent a total gastrectomy, which was a radical C operation. From postoperative month 4, he visited our hospital with multiple liver metastases and increased lymph node metastases. After chemotherapy with CDDP and 5-FU, CDDP and UFT was administered on an outpatient basis. The effect of this therapy was PD, therefore, docetaxel and 5'-DFUR combination chemotherapy was performed as second line therapy. After 2 courses of this therapy, the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. The patient has undergone 4 courses of this therapy and is maintaining a clinical PR. It is conceivable that docetaxel and 5'-DFUR combination chemotherapy is useful for patients with advanced and recurrent gastric cancer, even if they had been treated with 5-FU administration as first line therapy.     

A case of metastatic breast cancer achieving complete response by combination therapy with 5’-deoxy-5-fluorouridine and cyclophosphamide

Recently there have been several reports on the effectiveness of combination chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA) for treating recurrent breast cancer. We report a case in which treatment of local recurrence and lung metastases responded was remarkably effective by this combination chemotherapy. A 45-year-old woman underwent modified radical mastectomy for left breast cancer (T2N0M0) three years previously. Involvement of a left supraclavicular lymph node (ScLN) and multiple lung metastases were revealed 2 years and 6 months after the operation. First, we opted for systemic endocrine therapy with local irradiation for the lung metastases and ScLN. However the lung metastases were found to have increased on chest x-ray 2 months after treatment, showing progressive disease (PD). A locally recurrent new lesion sized 2 x 2 cm had also developed. Thus, we changed the treatment to combination chemotherapy with 5'-DFUR 800 mg/body and oral CPA 100 mg/body once a day. The lung metastases had disappeared on chest x-ray and the local recurrence was not palpable after 7 weeks of the new treatment. Thymidine phosphorylase (dThdPase) immunostaining of the primary tumor was strongly positive in almost all cancer cells. We discuss the mechanism of the increased efficacy of combination chemotherapy with 5'-DFUR and CPA.     

A case report of both CAF and docetaxel-resistant breast cancer responding to paclitaxel weekly therapy

A 58-year-old woman underwent CAF and docetaxel therapy for lung, liver and bone metastases from breast cancer operated on 14 years ago. Because of progressive disease due to secondary resistance to CAF and docetaxel, the patient was given three courses of paclitaxel therapy (60 mg/m2, day 1, 8, 15, repeated every 4 weeks). The paclitaxel weekly therapy brought about no adverse effects and remarkable effects against lung and liver metastases (PR). Although the duration of the response to the paclitaxel therapy was limited to about two months due to the progression of skull bone metastasis, paclitaxel weekly therapy may be effective against both CAF and docetaxel-resistant breast cancer.     

A case of pleural and mediastinal lymph node metastases from breast cancer effectively treated with fadrozole hydrochloride in combination with cyclophosphamide

A 63-year-old woman was diagnosed with pleural and mediastinal lymph node metastases 116 months after operation because of bilateral breast cancer. She was then treated with fadrozole hydrochloride (FH) (2 mg). Adriamycin (30 mg) administration into the pleural cavity was attempted, but did not prove effective. Thus, we tried to combine FH with cyclophosphamide (100 mg). After one month, chemoendocrine therapy relieved her complaints of cough and shortness of breath. CT revealed a remarkable decrease of pleural effusion and disappearance of mediastinal lymph nodes. She was alive 9 months after the treatment. Fadrozole hydrochloride in combination with cyclophosphamide is promising as an effective treatment in postmenopausal patients.     

Efficacy of combined chemoendocrine therapy with doxifluridine, cyclophosphamide, and fadrozole hydrochloride hydrate in a case of stage T4N3M1 breast cancer

A 66-year-old female presented with a swollen lump in the left breast. She was diagnosed as having advanced breast cancer of stage T4N3 (supraclavicular lymph node) M1 (bone). The administration of CEF and TAM failed to improve her condition. After the treatment regimen was changed to combined chemoendocrine therapy with CPA, EPI, 5'-DFUR, and MPA, the areas of bone metastases were reduced. However, MPA caused side-effects (acute obstruction of the lower limb), and thus the treatment was discontinued after 4 months. Subsequently, the treatment combination was changed to CPA, EPI, 5'-DFUR, and fadrozole hydrochloride hydrate. After one year of the treatment, a complete response (CR) was obtained with the disappearance of the supraclavicular lymph node and bone metastases. After EPI reached the maximum administration amount, the remaining CPA, 5'-DFUR and fadrozole hydrochloride hydrate oral administrations were continued. As of 3 years and 10 months after the onset of the chemoendocrine therapy, CR has been maintained with suppression of the primary and metastatic lesions, without degrading the patient's quality of life.     

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.     

Successful treatment of pleuritis carcinomatosa using combination therapy of 5'-DFUR, MPA and CPA as maintenance therapy

A 44-year-old female patient with inoperable, local advanced left breast cancer was treated with 3 cycles of high dose CAF therapy followed by combination therapy of 5'-DFUR, MPA and CPA. The patient was discharged after receiving 3 cycles of high-dose CAF therapy and continued to receive daily oral doses of 5'-DFUR (800 mg), MPA (800 mg), and CPA (100 mg) for 15 months. After 3 cycles of high-dose CAF therapy, tumor marker (CEA, CA 15-3) levels were reduced. Six months later, after 3 cycles of high-dose CAF therapy, the tumor marker levels were within the normal range. No serious side effects were observed during chemotherapy. The patient enjoyed a good quality of life. We thus confirmed that this combination regimen was effective as a maintenance therapy for local advanced breast cancer.     

Endocrine chemotherapy (high-dose toremifene + 5'-DFUR) found markedly effective for 2 cases of metastatic breast cancer]

Two cases of metastatic breast cancer are reported in which endocrine chemotherapy with Toremifene + 5'-DFUR proved markedly effective. Case 1: A 69-year-old female. After CAF therapy as a adjuvant chemotherapy, Tamoxifen and Tegafur had been administered. At the 5th postoperative year, multiple metastases to lung and a rise in the tumor marker were found. Since the patient was not desirous of intensive chemotherapy, administration of Toremifene 120 mg/day and 5'-DFUR 800 mg/day was initiated. The patient showed PR 9 months after and achieved CR 14 months later. Case 2: A 48-year-old female. CAF therapy for a total of 6 cycles was performed as adjuvant chemotherapy. The patient was administered Tamoxifen and followed. On bone scintigrams 3.5 years after surgery, an abnormal accumulation appeared in the left sternoclavicular joint, and an infiltrative tumor mass was formed in the skin of that region. Administration of Toremifene + 5'-DFUR was initiated. After 6 months, the infiltrative mass disappeared. These findings are suggestive of the effectiveness of this combined chemotherapy.     

A case of breast cancer with multiple organ metastases responding remarkably to combination therapy of CAF (cyclophosphamide, adriamycin and 5-FU), 5'-DFUR and MPA (medroxyprogesterone acetate)

A 52-year-old woman complaining of breast tumor was diagnosed as having advanced breast cancer (T4bN1M1-Stage IV), with metastasis of multiple organs (lung, liver, mediastinal and unilateral axillary lymph nodes) after which she underwent tumorectomy. Postoperative adjuvant therapy was performed using combined chemoendocrine therapy (CAF + 5'-DFUR + MPA). Following the endocrine therapy, the metastatic lesions of the liver and lung had disappeared. The adverse effects were not remarkable. Complete remission was continued for 2 years and 3 months, and the patient enjoyed a favorable quality of life.     

A long-term survivor with stage IV gastric cancer due to postoperative weekly paclitaxel and 5'-DFUR combination therapy

The patient was a 63-year-old woman who presented with upper abdominal discomfort. Type 3 gastric cancer in the midgastric region was diagnosed, and the patient underwent surgery. Because peritoneal metastasis and periaortic lymph node metastasis were confirmed, paraaortic lymph node metastasis, total gastrectomy and D 1 lymph node dissection were performed. Surgical and pathological findings were pType 3, pT 3(SE), sN 3, pP 1, sH 0, CY 1, Stage IV, and Cur C. After surgery, she was treated with five regimens of MTX/5-FU, TS-1 or DOC, but because progressive disease was confirmed, weekly paclitaxel and 5'-DFUR combination therapy was initiated as salvage therapy. Five months after the start of combination therapy, complete response was achieved, and combination therapy was continued for 19 more months. Since no recurrence was observed, therapy was terminated. No severe adverse reactions were observed. The patient has been recurrence-free for 25 months and remains alive as of 68 months after surgery. The present therapy may thus be effective in the treatment of previously treated Cur C advanced gastric cancer.     

A case of metastatic breast cancer responding to weekly paclitaxel and high-dose toremifene administrated alternately

A 64-year-old woman underwent muscle-preserving mastectomy for breast cancer in April 1999. She developed multiple lung metastases 3 months later. The metastases partially responded to 10 cycles of CAF (cyclophosphamide, adriamycin, 5-fluorouracil). However, her lung metastases worsened again 7 months later and CAF was not effective (progressive disease). We therefore began administration of low-dose paclitaxel (80 mg/m2/week) and high-dose toremifene (120 mg/day) alternately in April 2001. This alternative therapy brought a marked decrease in the lung metastases. After 4 cycles of this treatment, lung metastatic findings had disappeared from her chest X-ray. This alternative therapy is potentially effective against metastatic breast cancer.     

Placental site trophoblastic tumor with multiple metastases and complete response to salvage BEP regimen: a case report and review of the literature

Placental site trophoblastic tumor is a rare form of gestational trophoblastic disease, derived from invasive implantation site (intermediate) trophoblastic cells. It is frequently resistant to chemotherapy. Patients with metastases, however, frequently have progressive disease and die despite surgery and multiagent chemotherapy. In this case, a 24-year-old woman was referred because of intermittent vaginal bleeding episodes for 5 months following delivery. Multiple metastases in lungs, liver, kidneys, breast, pancreas, and adrenal and thyroid glands were detected. Combination therapy including surgery and multiagent chemotherapy was planned. Hysterectomy and pelvic lymph node dissection were performed. All metastatic lesions disappeared with EMA-CO treatment. However four courses of BEP regimen, salvage therapy, was performed for plateauing hCG level. Surgery and multiagent chemotherapy seem mainstay of treatment of cases having multiple metastases of PSTTs.     

A case of multiple pulmonary metastases from duodenal cancer showing partial response using 5'-DFUR and a small dose of MMC]

A 77-year-old female with primary duodenal cancer had undergone pancreatoduodenectomy in May, 1989. Postoperative chemotherapy was done in combination with MMC (mitomycin C), lentinan and UFT (combined medicine of tegafur and uracil). In August, 1991, the patient complained of a cough and then was examined for multiple pulmonary metastases from duodenal cancer by chest X-ray and CT-scan. Then, she received 5'-DFUR (400-800 mg) and MMC (total 6 mg). Two months from the start of this therapy, the cough almost vanished and pulmonary lesions were diminished markedly. For about five months, this case corresponded to partial response (PR) according to the response criteria proposed by Koyama-Saitoh. The side effects of 5'-DFUR were diarrhea and anorexia. Therefore, we think that 5'-DFUR and a small dose of MMC yielded a partial response to multiple pulmonary metastases from duodenal cancer.     

A case of advanced gastric cancer--efficacy of combination therapy of doxifluridine and weekly paclitaxel

A 65-year-old man underwent distal gastrectomy for advanced gastric cancer. Histological examination revealed that a lymph node metastasis extended to the para-aortic nodes. After operation, he was treated with TS-1 as first-line chemotherapy. After 10 months of the first-line chemotherapy, the lymph node swelling increased in size, and new lesions were detected. Then, the patient was treated by combination therapy of doxifluridine and weekly paclitaxel. Weekly paclitaxel administration (PTX 80 mg/m(2), 2 consecutive weeks, 1 week break) and oral administration of doxifluridine (600 mg/m(2), 14 consecutive days) were performed as the second-line chemotherapy. After 2 courses, abdominal CT scan showed a remarkable reduction of the para-aortic lymph nodes. The second-line chemotherapy was continued until the 7th course, then stopped without progression of the disease, and the patient maintained good quality of life. PTX/5'-DFUR combination therapy was thought to be an effective chemotherapy for advanced gastric cancer.     

Combination of 5'-DFUR and MMC for recurrent rectal cancer with pulmonary metastasis]

We report a 68-year-old man with rectal cancer and recurrent pulmonary metastasis treated with concomitant 5'-DFUR + MMC, which resulted in an extreme reduction of the lesion. The initial pulmonary metastases were treated by pneumonectomy, but 32 months later the patient again showed a pulmonary metastasis. Thus, from July 1997, he was treated with 5'-DFUR (800 mg/day) + MMC (4 mg/2 weeks). After 3 months of therapy, the chest CT examination showed an extreme reduction of the pulmonary lesion, and at 5 months the lesion was even smaller. Presently, after 7 months of therapy, the lesion remains stable. His CEA level is 1.0-2.6 ng/ml. After 4 months of treatment he had mild anorexia, which was alleviated by reducing the 5'-DFUR to 600 mg/day. No other adverse reaction was observed; the therapy was safely conducted on an outpatient basis.     

Two cases of effective weekly paclitaxel administration for metastatic breast cancer]

We report two cases of effective weekly paclitaxel (TXL) administration for metastatic breast cancer. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. Case 1: A 66-year-old woman was treated with adriamycin, cyclophosphamide, doxifluridine (5'-DFUR), fadrozole, medroxyprogesterone acetate (MPA) and pamidronate for pleural, mediastinal and supraclavicular lymph nodes and skull metastases. She complained of hoarseness and supraclavicular and mediastinal lymph nodes had developed, for which she received weekly TXL administration. Metastatic lymph nodes had disappeared 3 months after administration. Case 2: A 61-year-old woman was treated with CMF therapy, 5'-DFUR, tamoxifen, MPA fadrozole and pamidronate for bone metastasis and local recurrence. She received weekly TXL administration for an axillary recurrence and contralateral supraclavicular lymph node metastases. Metastatic and recurrent lesions had disappeared 3 months after administration. The toxic events were leukopenia (grade 1) and peripheral neuropathy (grade 1). No major adverse effects were observed in either case.     

A case of effective chemotherapy using CAF followed by docetaxel for advanced breast cancer

A huge mass measuring 13 x 12 cm and wide cutaneous edema were detected in the right breast of a 51-year-old woman. Under a diagnosis of locally advanced breast cancer (T4bN2M1, stage IV) with liver metastases, we attempted sequential neoadjuvant chemotherapy. After three courses of CAF therapy (cyclophosphamide, doxorubicin (DXR), 5-FU), the primary tumor was decreased by 56% and the liver metastases had disappeared. A minor pathologic response was observed. Subsequently, three courses of docetaxel (TXT) administration were carried out. The primary tumor was then decreased by 75% and the axillary metastases had disappeared. Histopathological examination showed gross viable tumor cells in the residual tumor and positive axillary lymph nodes. The only toxic effect was nausea (grade 1) and no major adverse effects were observed. Neoadjuvant chemotherapy with sequential DXR followed by TXT is a useful treatment for locally advanced breast cancer.     

A case of effective paclitaxel therapy for adriamycin resistant metastatic breast cancer with brain metastases

A 36-year-old woman was referred to our hospital because of a right breast lump. Chest computed tomography revealed pulmonary metastases with lymphangitis carcinomatosa. Additional examination revealed liver metastases and axillary and cervical lymph node metastases. The patient was started on CA therapy (cyclophosphamide 900 mg, adriamycin 90 mg). A minor response was observed in the pulmonary metastases after two courses but new brain metastases were detected. We then tried paclitaxel administration (260 mg). A partial response was observed in the brain and pulmonary metastases. Thus, paclitaxel administration was continued on a weekly basis (120 mg) and the brain and pulmonary metastases continued to diminish. The primary breast cancer, liver metastases and axillary and cervical lymph node metastases were disappeared. Whole brain radiation was done with weekly paclitaxel administration and the brain metastases were diminished even more. Paclitaxel is as a radiosensitizer and seems to have a strong antineoplastic effect with concurrent radiation.