Biomedical subjects

I Adachi

Publications and source records attributed to I Adachi.

At least 109 records · Page 6Linked to original sources

PubMed1999

Therapy-related leukemia and myelodysplastic syndrome in breast cancer patients treated with cyclophosphamide or anthracyclines.

BACKGROUND: Accumulation of data regarding therapy-related leukemia (TRL) or myelodysplastic syndrome (t-MDS) is critical for assessing the risk of developing such diseases and for subsequent decision-making processes for better treatment. METHODS: We evaluated the clinical characteristics of patients with TRL/t-MDS diagnosed at the National Cancer Center Hospital between January 1989 and September 1997. This report is concerned with those patients who initially had been treated with chemotherapeutic agents for breast cancer. RESULTS: Thirteen patients (median age, 55 years) developed TRL (n = 4) or t-MDS (n = 9). The median interval between the development of TRL/t-MDS and initial treatment was 94 months (range 23-190 months). For the primary therapy, all patients had received intense and prolonged treatment with cyclophosphamide (CPA) and/or anthracyclines including doxorubicin (DOX), with a median cumulative dose of 55 g/body (range 16.4-288.5 g) for CPA and 480 mg/m2 (range 395-625.5 mg/m2) for DOX. Seven patients were subsequently treated by chemotherapy and one received an allogeneic bone marrow transplantation. CONCLUSIONS: Clinicians must remain alert to the risks associated with unproven medical practices which include long-term administration of alkylating agents. Selected patients with TRL/t-MDS may respond to intense salvage combination chemotherapy.

Adult↗

PubMed1999

[Evaluation of 99mTc-MAG3 (mercaptoacetyltriglycine) renography for pediatric patients].

It is difficult to evaluate renal function with 99mTc-MAG3 renography in both adult and pediatric patients. We examined 109 pediatric patients with various renal diseases using 99mTc-MAG3 renography. Tenal diseases were classified as follows: 9 vesicoureteral reflux, 4 ureteropelvic junctional stenosis, 3 double pelvis, 23 hydronephrosis, 4 glomerulonephritis, 4 nephrotic syndrome, 24 hemolytic uremic syndrome, 10 others; and 24 patients without abnormal findings on other examinations. After hydration and sedation, 100-200 MBq of 99mTe-MAG3 was injected intravenously. All patients were placed in the supine position, and dynamic data acquisition at 12 sec/frame x 100 frames was performed from the back. The renograms were prepared with the ROIs (regions of interest) set to include the entire kidney. Tmax and T1/2 of renograms were measured for 26 kidneys with no abnormal findings. The correlations between Tmax or T1/2 and age (days after birth) were determined by a linear or logarithmic function. The logarithmic function (Y = 7.49 - 0.56 logeX, r2 = 0.134) yielded a higher correlation than did the linear function (Y = 5.16 - 0.00194X, r2 = 0.089) between Tmax and age. For T1/2 and age (days after birth), the linear function (Y = 8.07 - 0.00451X, r2 = 0.222) yielded a higher correlation than the logarithmic function (Y = 11.9 - 0.986 logeX, r2 = 0.192). Our findings suggest that prolonged Tmax is normalized more rapidly than T1/2 after birth in infants. A delayed excretion phase is not suggestive of renal dysfunction, but is characteristic of renograms in pediatric patients. Abnormality was detected in all patients with hydronephrosis using 99mTc-MAG3 renography. On the other hand, a quantitative study was required because renography detected no abnormality for some of patients with disorders of renal parenchyma.

Adolescent↗

PubMed1999

[Assessment of left ventricular function by electrocardiogram-gated myocardial single photon emission computed tomography using quantitative gated single photon emission computed tomography software].

Electrocardiogram (ECG)-gated myocardial single photon emission computed tomography (SPECT) can assess left ventricular (LV) perfusion and function easily using quantitative gated SPECT (QGS) software. ECG-gated SPECT was performed in 44 patients with coronary artery disease under post-stress and resting conditions to assess the values of LV functional parameters, by comparison to LV ejection fraction derived from gated blood pool scan and myocardial characteristics. A good correlation was obtained between ejection fraction using QGS and that using cardiac blood pool scan (r = 0.812). Some patients with myocardial ischemia had lower ejection fraction under post-stress compared to resting conditions, indicating post-stress LV dysfunction. LV wall motion and wall thickening were significantly impaired in ischemic and infarcted myocardium, and the degree of abnormality in the infarcted areas was greater than in the ischemic area. LV functional parameters derived using QGS were useful to assess post-stress LV dysfunction and myocardial viability. In conclusion, ECG-gated myocardial SPECT permits simultaneous quantitative assessment of myocardial perfusion and function.

Electrocardiography↗

PubMed1999

[Quantitative assessment of 201Tl-SPECT in tumors of bone and soft tissue].

201Tl-SPECT was performed to diagnose the malignancy of bone and soft tissue tumors by visual and quantitative assessment in 48 patients (17 malignant lesions and 31 benign lesions). SPECT images were obtained in the early phase (15 min after injection) and the delayed phase (240 min). By visual assessment a tumor was considered malignant if high accumulation was found in the tumor in the early phase and the accumulation was confirmed in the delayed phase. Tumors which did not meet these criteria were considered benign. For quantitative assessment, the ROI (region of interest) accumulation ratios of the tumor to the contralateral normal tissue in the early phase (ER) and in the delayed phase (DR), the ROI accumulation ratio of the delayed phase to the early phase of the tumor (Td/Te), and the ROI accumulation ratio of the delayed phase to the early phase of the contralateral normal tissue (Nd/Ne) were obtained. Sixteen patients with malignant tumors each had a high accumulation each but 12 of 31 benign lesions had no high accumulation on visual assessment. Furthermore, the accuracy was 85.4%, sensitivity 94.1%, and specificity 80.6%. Quantitative assessment was performed for 36 cases of high accumulation. The ER of malignant and benign lesions was 5.51 +/- 3.73 and 2.75 +/- 2.17, respectively, and the ER of malignant lesions was significantly higher than that of benign lesions. The DR did not demonstrate a significant difference. If the tumor having an ER greater than 3.9 was assumed to be malignant, the accuracy for differentiating malignant lesions from benign lesions was 85.4%. The Td/Te of benign lesions (0.97 +/- 0.28) was higher than that of malignant lesions (0.77 +/- 0.09). The Nd/Ne of normal tissue which contained muscles in both lesions were higher than 1.4. In conclusion, 201Tl-SPECT was very useful for the differential diagnosis of benign or malignant bone and soft tissue tumors. The ER was important for quantitative assessment, but a delayed image was necessary for visual assessment.

Adolescent↗

PubMed1999

[Visualization of normal organs in whole-body FDG-PET imaging].

It is important to know FDG accumulation in the normal distributions for interpreting whole-body PET imaging for tumor detection. Twenty-eight normal subjects were studied with whole-body PET imaging and were examined the intensity of FDG uptake in major organs and the factors which caused it's variety. Emission images were acquired and images were reconstructed without attenuation correction. The intensity of FDG uptake was classified into 4 grades visually. No accumulation was found in the thyroid, the esophagus and the spleen. The oral cavity, the liver, the stomach, and the colon were visualized in all subjects. The laryngeal muscle, the cervical muscle, and the heart accumulated FDG with various grade from 1 to 4 grades. No association was found between the intensity of uptake in the organs and volunteer's age. The fasting time was shorter in volunteers whose heart showed "high" grade than those showed less accumulation (p < 0.05). Serum concentration of free fatty acid was significantly lower in them, too (p < 0.05). Various FDG uptake was observed in many organs, especially the laryngeal muscle, the cervical muscle, and the heart. In our study, there was no facter which caused FDG uptake in organs except for the fasting time and the value of free fatty acid in the heart. Such analysis of whole-body FDG distributions in the normal subjects is valuable for tumor detection with FDG-PET.

Adult↗

PubMed1999

Serum levels of soluble intercellular adhesion molecule-1 and E-selectin in metastatic breast carcinoma: correlations with clinicopathological features and prognosis.

Cellular adhesion molecules have been demonstrated to play an important role in the progression and metastasis of malignancies. We determined the serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) by enzyme-linked immunosorbent assay in 49 Japanese patients with metastatic breast cancer. Significantly high concentrations of sICAM-1 and sE-selectin were found in the patients with liver and/or bone metastases (both P<0.05). The mean serum sICAM-1 levels were significantly higher in patients with two or more metastatic sites compared to those with one metastatic site (P=0.001). A significant correlation was found between serum sICAM-1 (P=0.0001) and sE-selectin (P<0.0001) and the interleukin (IL)-6 levels. The patients who did not respond to chemo/ endocrine therapy showed significantly higher sICAM-1 and sE-selectin levels compared with those who responded to therapy (P=0.0004, P=0.02, respectively). Moreover, high sICAM-1 levels predicted a significantly poorer overall survival in both univariate and multivariate analyses. Our results suggest that the shedding of sICAM-1 or sE-selectin may enhance the metastatic process by escaping from host immune surveillance. The serum sICAM-1 level may help to predict the patient response to chemo/endocrine therapy and may be of prognostic significance in metastatic breast cancer patients.

Adult↗

PubMed1998

A phase I trial of docetaxel and 5-day continuous infusion of 5-fluorouracil in patients with advanced or recurrent breast cancer.

To determine the maximum-tolerated doses (MTDs), the dose-limiting toxicities (DLTs) and the recommended doses for further trials of docetaxel in combination with a 5-day continuous infusion of 5-fluorouracil (5-FU) in advanced or recurrent breast cancer patients who had been treated previously with at least one chemotherapeutic regimen, patients were treated with docetaxel as a 1-h infusion on day 1 followed by 5-FU as a continuous infusion on days 1 through 5 every 3-4 weeks. Three or six patients were assessed at the following escalating dose levels of docetaxel/5-FU per day: 40/150, 40/300, 50/300, 50/500 and 60/500 mg m(-2). Nineteen patients entered this trial, of whom 18 could be assessed for adverse event and therapeutic efficacy. The DLTs were neutropenia and diarrhoea. The MTDs were 60 mg m(-2) of docetaxel on day 1 and 500 mg m(-2) per day of 5-day continuous infusion of 5-FU. One of 18 patients achieved a complete response and eight achieved partial response (over all response rate: 50%). The recommended doses of docetaxel and 5-day continuous infusion of 5-FU for a phase II trial are 50 mg m(-2) and 500 mg m(-2) per day every 3 or 4 weeks.

Adult↗

PubMed1998

Clinical characteristics of patients with metastatic breast cancer with complete remission following systemic treatment.

BACKGROUND: Patients with metastatic breast cancer (MBC) have variable clinical courses. The purpose was to describe the clinical characteristics of MBC patients with complete remissions (CR) following systemic treatment. METHODS: We analyzed 315 consecutive MBC patients treated with several types of systemic treatments at the National Cancer Center Hospital between January 1988 and December 1993. RESULTS: The median survival time (MST) and median progression-free survival were 28.0 and 17.1 months, respectively. Forty patients were defined as 'first-CR' following initial or second-line systemic treatment and the majority of them had a good performance status, low number of metastatic sites and low incidence of liver involvement. Nine of 40 patients with first-CR continued progression-free 5 years after beginning systemic treatments. The major sites of metastasis were the lung and bone and there were no cases with liver metastasis. Five patients received standard doxorubicin-containing combination chemotherapy with or without tamoxifen. Two of these nine patients remain progression free in first-CR. Three of them remained in first-CR after 5 years and died of progressive breast cancer and two others died of unrelated causes. Two patients relapsed after obtaining a first-CR for at least 5 years and remain alive with active metastatic disease. The MST and median progression-free survival of nine patients were 10.6 and 9.0 years, respectively. These nine patients represented 22.5% of all first-CR patients and 3.2% of the total patients. CONCLUSIONS: Although MBC is commonly recognized to be an incurable disease, a small percentage of patients clearly are alive and progression free for prolonged periods after initiation of systemic treatments.

Adult↗

PubMed1998

Construction and validation of a practical prognostic index for patients with metastatic breast cancer.

PURPOSE: To identify the readily available prognostic factors most helpful in predicting survival and to construct and validate a prognostic index for metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Data from 233 MBC patients, accrued on a multiinstitutional randomized phase III trial (Japan Clinical Oncology Group [JCOG] study 8808), were analyzed to identify significant prognostic factors and a prognostic index was constructed by incorporating these prognostic factors. For validation of the prognostic index, another data set from 315 consecutive MBC patients, who had been treated with standard anthracycline-containing regimens, was analyzed. RESULTS: In multivariate regression analyses, history of adjuvant chemotherapy (ADJCT) (P = .0005), presence of distant lymph nodes (DLNs) (P = .0117) and liver (HEP) (P = .0099) metastases, elevation of serum lactate dehydrogenase (LDH) (P < .0001), and shorter disease-free interval (DFI) (P < .0001) significantly contributed to poorer survival. The prognostic index was constructed as follows: Prognostic Index = ADJCT (not received = 0, received = 1) + DLNs (absent = 0, present = 1) + HEP (absent = 0, present = 1) + LDH (< or = one times normal = 0, > one times normal = 1) + DFI (> or = 24 months = 0, < 24 months = 2). With this prognostic index, patients could be stratified into three risk groups. The median survival times (MSTs) of low-, intermediate- and high-risk groups were 45.5, 24.6, and 10.6 months, respectively (P < .0001). This prognostic index was applied to the validation patients. The respective MSTs for each risk group were 49.6,22.8, and 10.0 months (P < .0001). CONCLUSION: ADJCT, DLNs, HEP, LDH, and DFI were important prognostic factors for MBC patients. The prognostic index readily enables MBC patients to be stratified into three risk groups and is worth considering for future clinical trials.

Analysis of Variance↗

PubMed1998

Microdialysis assessment of 5-fluorouracil release from thermosensitive magnetoliposomes induced by an electromagnetic field in tumor-bearing mice.

The current study was designed to evaluate the properties of thermosensitive magnetoliposomes (TMs), a new drug carrier proposed by the authors, in an electromagnetic field pertaining to their selective heating and drug release under an in vivo condition. TMs containing 5-fluorouracil (5-FU) were prepared by reverse-phase evaporation, injected into the tumor mass of B 16-BL6 melanoma in mice, and selectively heated by a 500-kHz electromagnetic field. The release profile of 5-FU from TMs was examined by using a microdialysis technique. The temperature of TMs in the tumor was effectively elevated to 42 degrees C and maintained at this temperature, overcoming the "cooling effect" of blood flow and surrounding tissues. The release kinetics of 5-FU from TMs was successfully analyzed by physiological modeling, which allows the prediction of intratumor drug concentrations during electromagnetic field exposure under various conditions. In conclusion, this study first demonstrated an in vivo evidence for the electromagnetic field-induced thermosensitive release of a drug from TMs in a tumor with the use of microdialysis.

Animals↗

PubMed1998

[Clinical usefulness of scatter and attenuation correction for brain single photon emission computed tomography (SPECT) in pediatrics].

This investigation was undertaken to study clinical usefulness of scatter and attenuation correction (SAC) of brain SPECT in infants to compare the standard reconstruction (STD). The brain SPECT was performed in 31 patients with 19 epilepsy, 5 cerebro-vascular disease, 2 brain tumor, 3 meningitis, 1 hydrocephalus and psychosis (mean age 5.0 +/- 4.9 years old). Many patients was necessary to be injected sedatives for restraining body motion after Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was injected at the convulsion or rest. Brain SPECT data were acquired with triple detector gamma camera (GCA-9300 Toshiba Japan). These data were reconstructed by filtered backprojection after the raw data were corrected by triple energy windows method of scatter correction and Chang filtered method of attenuation correction. The same data was reconstructed by filtered backprojection without these corrections. Both SAC and STD SPECT images were analyzed by the visual interpretation. The uptake ratio of cerebral basal nuclei was calculated by the counts of the thalamus or lenticular nuclei divided by the cortex. All images of SAC method were excellent than that of STD method. The thalamic uptake ratio in SAC method was higher than that of STD method (1.22 +/- 0.09 > 0.87 +/- 0.22 p < 0.01). The lenticular nuclear uptake ratio in SAC method was higher than that of STD method (1.26 +/- 0.15 > 1.02 +/- 0.16 p < 0.01). Transmission scan is the most suitable method of absorption correction. But the transmission scan is not adequate for examination of children, because this scan needs a lot of time and the infants are exposed by the line source radioisotope. It was concluded that these scatter and absorption corrections were most suitable method for brain SPECT in pediatrics.

Adolescent↗

PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗

PubMed1997

The Clinical Utility of Docetaxel in Adriamycin-Resistant Breast Cancer.

Taxanes were developed as third-generation anticancer agents following methotrexate and adriamycin, two major chemotherapeutic agents for breast cancer. These agents have been studied to confirm antitumor effects in anthracycline-resistant patients and patients with liver metastasis. In this study, we examined the usefulness of taxanes, especially docetaxel, in chemotherapy for breast cancer by reviewing results in Japan and other countries. In a late phase II clinical study in Japan, the administration of 60 mg/m(2) /hr/3-4w of docetaxel (DOC) reduced tumor size in 50.4% of patients. In 6% of these patients, complete response (CR) was achieved. The duration of response was 14.7 weeks. Thirty-five percent of 26 primary adriamycin(ADM)-resistant patients responded to DOC treatment (CR:4.0%).

Journal Article↗

PubMed1997

Immunological and histological disorders in cats experimentally infected with feline immunodeficiency virus subtype B (TM2 stain).

Three conventional cats were experimentally infected with subtype B (TM2 strain) of FIV, and two conventional cats served as controls. The infected cats were examined immunologically 99-176 weeks post FIV inoculation (wpi) and histologically at 130 wpi. Two of the three infected cats exhibited lower CD4/CD8 T cell ratios and hypergammaglobulinemia compared with two control cats. Further, all the infected cats showed morphological changes in popliteal lymph nodes such as lymphoid depletion, atrophy and plasma cell hyperplasia. In addition, apoptosis was induced in peripheral blood mononuclear cells (PBMC) from the FIV-infected cats after in vitro culture for one or two days, but not in PBMC from uninfected cats. These observations indicate that FIV subtype B has the potential to induce some immunological and histological disorders in cats.

Animals↗

PubMed1997

Evaluation of uptake and release of technetium-99m MIBI SPECT of pulmonary and mediastinal lesions.

We evaluated the uptake and release of Tc-99m MIBI in 7 benign and 30 malignant pulmonary and mediastinal lesions. Of the 37 patients, 13 underwent surgery; malignant involvement was examined in 21 mediastinal lymph nodes. Tl-201 SPECT was also performed in 10 patients. Tc-99m MIBI SPECT studies were performed on transverse SPECT images acquired 30 minutes and 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A). Regions of interest were set in the area of abnormal uptake of Tc-99m MIBI and in an area of normal tissue in the contralateral lung. The uptake ratio of the lesion in the contralateral normal lung was obtained on the early image (early ratio; ER) as well as the delayed image (delayed ratio; DR). The benign lesions showed significantly lower ER (1.6 +/- 0.3) and DR (1.4 +/- 0.4) than the malignant lesions (1.9 +/- 0.5 and 1.8 +/- 0.5, respectively; both p < 0.05). There was no significant difference in the retention index (RI), calculated as RI = (DR-ER)/ER x 100. The DR obtained with Tl-201 SPECT images was significantly higher than that obtained with Tc-99m MIBI SPECT (p < 0.05). For the detection of mediastinal lymph node metastases, the early images showed sensitivity, specificity, and accuracy of 85.7%, 100%, and 95.2%, respectively, for the delayed images these values were 85.7%, 92.9%, and 90.5%, respectively. These results suggest that the uptake ratio of Tc-99m MIBI is a useful index in assessing benign or malignant pulmonary and mediastinal lesions.

Aged↗

PubMed1997

Iodine-123 metaiodobenzylguanidine myocardial scintigraphy for prediction of response to beta-blocker therapy in patients with dilated cardiomyopathy.

This study was performed to evaluate whether iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predict the response to beta-blocker therapy in patients with nonischemic dilated cardiomyopathy (DCM). Beta-Blocker therapy is effective in some patients with DCM. MIBG myocardial scintigraphy has also been suggested to be useful in evaluating the severity of myocardial damage in DCM. However, no data exist on whether MIBG imaging can be used to predict which patients with DCM will respond to beta-blocker therapy. We prospectively evaluated whether MIBG myocardial imaging was useful in predicting responses to beta-blocker therapy in patients with DCM. MIBG imaging was performed in 45 patients with DCM (35 men, 10 women, aged 13 to 68 years) before the start of bisoprolol. The heart to mediastinum (H/M) MIBG uptake ratio was evaluated on initial and delayed images, and the percent washout rate of myocardial MIBG was also obtained from these data. Of the 45 patients, 30 (67%) responded to beta-blocker therapy, whereas 2 were resistant and 13 showed progression of heart failure or died of heart failure. By logistic regression analysis, the H/M uptake ratio on delayed images was seen to be a good predictor of the response to beta-blocker therapy with a threshold of 1.7 (sensitivity = 91%, specificity = 92%, accuracy = 91%, positive and negative predictive value = 97% and 80%, respectively). These results indicate that an H/M ratio > 1.7 on the delayed MIBG myocardial scintigraphic images provides a useful indication of whether patients with DCM will respond to beta-blocker therapy.

3-Iodobenzylguanidine↗

PubMed1997

Do repolarization abnormalities in hypertrophic cardiomyopathy represent impaired fatty acid utilization? An observation with QRST isointegral maps.

To identify the clinical significance of the isointegral body surface map of the QRST interval (QRST map) and the occurrence of repolarization abnormalities in patients with hypertrophic cardiomyopathy (HCM), the QRST map and signal-averaged electrocardiogram were evaluated in 50 patients with HCM, in 33 of whom the results were compared with nuclear images both for radioiodine-labeled fatty acid metabolism and for radiothallium perfusion. The QRST departure map was used to determine two parameters of difference between patient and control recordings: the subnormal area (the number of lead points at which the departure index values were negative and lay more than 2 SDs from the mean of the normal control group) and the subnormal minimum (the absolute value of the minimum in the departure map). Late potentials were detected in 6 (12%) of the 50 patients; they were observed in 3 of the 5 patients with dilated-phase HCM but in only 3 (7%) of the other 45 patients. The subnormal area and minimum values were lower in nonobstructive HCM than in dilated-phase HCM. Of the 33 patients examined by myocardial imaging, 28 (33%) had a filling defect or decreased uptake, as shown on fatty acid metabolic images, and 10 of the 28 also showed abnormal myocardial perfusion images, while the 18 others showed normal perfusion images. These 28 patients showed significantly larger values of the subnormal area and minimum than patients with normal results in both image tests, regardless of whether or not myocardial perfusion imaging abnormalities were present. The localization of filling defects or of decreased uptake presented in fatty acid metabolic images corresponded to the position of the minimum on the QRST departure map. These results suggest that the QRST map is useful for detection of repolarization abnormalities in HCM and that these abnormalities are highly related to impaired fatty acid utilization of the myocardium.

Adolescent↗

PubMed1997

A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group.

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.

Adult↗