pirarubicin and Breast-Neoplasms

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials, Phase I as Topic; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphoma; Mesothelioma

Topics: Aclarubicin; Anthraquinones; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Cell Survival; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Heart; Humans; Idarubicin; Leukemia; Menogaril; Mitoxantrone; Naphthacenes; Nogalamycin; Sarcoma; Structure-Activity Relationship

Observation indexes used to evaluate the effect of dexrazoxane-anthracycline combinations in breast cancer often only take into account the clinical symptoms, or left ventricular ejection fraction (LVEF), biomarkers [such as creatine kinase MB (CK-MB), brain natriuretic peptide (BNP) and cardiac troponin T (cTnT)], or tumor recurrence rate, improvement of autonomic nerve function or economic benefits. This study aimed to evaluate the effect of dexrazoxane on the changes of mechanical properties of right ventricular myocardium in patients who underwent pirarubicin chemotherapy with three-dimensional speckle-tracking imaging (3D-STI).. A total of 64 breast cancer post-operation patients who received pirarubicin chemotherapy were randomly divided into two groups: the experimental group (with dexrazoxane added) and the control group (without dexrazoxane). The mechanical properties of the right ventricular myocardium were monitored by 3D-STI before and after chemotherapy. The levels of serum hypersensitive troponin I (hs-cTnI) and N-terminal B-type pro-natriuretic peptide (NT-proBNP) as well as conventional echocardiographic parameters were also measured.. After chemotherapy, right ventricular global longitudinal strain (RVGLS) and right ventricular global area strain (RVGAS) were significantly reduced in both groups (P<0.05). There was a significant difference between the two groups (P<0.05).. Dexrazoxane can alleviate the toxicity of pirarubicin in the right ventricular myocardium. 3D-STI is a potential new method for early and accurate evaluation of the mechanical properties and functional changes of the right ventricular myocardium.

Topics: Biomarkers; Breast Neoplasms; Dexrazoxane; Doxorubicin; Humans; Myocardium; Sexually Transmitted Diseases; Stroke Volume; Ventricular Function, Left

Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS), respectively. Our study found that NACT with DTC regimen and DEC regimen were both very effective in treatment of BC. However, THP-based combination therapy was associated with significantly lower incidence of cardiac toxicity, myelosuppression, nausea, and vomiting.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Docetaxel; Doxorubicin; Drug-Related Side Effects and Adverse Reactions; Epirubicin; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Taxoids

This study aimed to evaluate the efficacy and safety of adjuvant chemotherapy with pirarubicin plus capecitabine (AX regimen) in Chinese node-negative breast cancer (BCa) patients. Two hundred eighty Chinese pT1-2N0M0 BCa patients under 70 years of age were equally and randomly assigned to receive four cycles of adjuvant therapy with the AX regimen or pirarubicin and cyclophosphamide (AC regimen) between January 2010 and May 2011. End points included overall survival (OS), disease-free survival (DFS), chemotherapy-induced toxicities, and quality of life (QoL). The 4-year DFS (AX vs. AC, 93.6 vs. 92.9 %, P = 0.761) and OS (97.1 vs. 96.4 %, P = 0.965) were similar between the two treatment arms. The AX group, compared to the AC group, experienced significantly less frequent grade III/IV vomiting (11.4 vs. 26.4 %, P < 0.001), whereas the incidence of other grade III/IV chemotherapy-associated toxicities was comparable between the two groups (all P values >0.05). Use of the AX regimen was associated with significantly higher QoL scores in the domains of physical, role, and social functions than the AC regimen (P values <0.05), although the two regimens were similar in the domains of emotional and cognitive functions (all P values >0.05). In comparison with the AC regimen, AX adjuvant chemotherapy is equally beneficial for node-negative BCa patients younger than 70 years with respect to OS and DFS. The AX regimen is primarily advantageous over the AC regimen based on less frequent severe toxicities and better health-related QoL.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Chemotherapy, Adjuvant; China; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Middle Aged

To compare the chemosensitivity of pirarubicin (THP) and epirubicin (EPI) in primary breast cancer (PBC) cells so as to examine their differential chemosensitivity to THP and EPI by CD-DST (collagen gel droplet embedded culture-drug sensitivity test) system; To detect the differences in the short-term clinical efficacy and side effects between TAC (docetaxel + pirarubicin + cyclophosphamide) and TEC (docetaxel + epirubicin + cyclophosphamide) as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF (cyclophosphamide + pirarubicin + fluorouracil) and CEF (cyclophosphamide + epirubicin + fluorouracil) as the chemotherapy regimens in breast cancer; To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer.. From January 2008 to January 2009, a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients inIIb-IIIc phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axillary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups.. There was no significant difference of chemosensitivity between THP and EPI in PBC cells (P = 0.743); The overall response rate (RR) of neoadjuvant chemotherapy was 87.8%; the clinical objective responses, pathologic complete remission (pCR), clinical complete remission (cCR), clinical partial remission (cPR) and stable disease (SD) of groups TAC and TEC were 88.7%, 11.3%, 28.2%, 60.6%, 11.3% vs 86.8%, 10.3%, 26.5%, 60.3%, 13.2% respectively. There was no significant difference between two groups (P > 0.05). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0.05). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that in the TEC group (46.5% vs 66.2%, P = 0.019); There was no significant difference in 5-year disease-free survival rate (79% vs 78%) and overall survival rate between two groups (85% vs 82%, P > 0.05).. There were no significant differences in chemosensitivity, clinical efficacy of neoadjuvant chemotherapy, side effects or long-term efficacy between THP and EPI. Both pirarubicin and epirubicin may be used as conventional chemotherapy in breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Retrospective Studies; Tamoxifen; Young Adult

To compare the efficacy and toxicity of neoadjuvant chemotherapy of docetaxel with paclitaxel plus pirarubicin hydrochloride (THP) and cyclophosphamide (CTX) in locally advanced breast cancer (LABC).. A total of 97 LABC cases were randomly divided into 2 groups: docetaxel group (n = 49, taxotere plus THP & CTX) and paclitaxel group (n = 48, paclitaxel plus THP & CTX). Neoadjuvant chemotherapy had four cycles of 21 days each.. The clinical and pathological complete remission rates of docetaxel group was 28.6% and 26.5% respectively. They were significantly higher than those of paclitaxel group (10.4% and 8.3%). Furthermore the pathological negative rate of regional lymph node in docetaxel group was also significantly higher than that of paclitaxel group (40.6% vs. 12.9%). However, grade III-IV blood system toxic reaction was found in 71.4% cases, grade II-IV liver dysfunction in 53.1% cases and edema in 24.5% cases among docetaxel group. They were higher than those among paclitaxel group (46.9%, 27.1% & 4.2%).. Compared with paclitaxel, the combined regimen of docetaxel plus THP and CTX offers better outcomes for locally advanced breast cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Docetaxel; Doxorubicin; Female; Humans; Middle Aged; Neoplasm Staging; Paclitaxel; Taxoids; Young Adult

The purpose of this study is to compare the efficacy of weekly paclitaxel to every-3-week schedule in terms of pathologic response and toxicity which caused treatment delay in primary chemotherapy of breast cancer. After pretreatment of two cycles of cyclophosphamide/ pirarubicin/ fluorouracil (cyclophosphamide 500 mg/m(2) days 1, 8; pirarubicin 35 mg/m(2) days 1, 8; 5-Fu 200 mg/m(2) day ci day 1-28, every 4 weeks), 219 women with histologically confirmed T(1-3) N(0-2) M(0) invasive breast cancer, whose vertical diameters production of breast tumor reduced not more than 75%, were randomized to receive four cycles of Pq3wC (arm A: paclitaxel 175 mg/m(2) day 1, carboplatin AUC 6 d1, every 3 weeks) or Pq1wC (arm B: paclitaxel 60 mg/m(2) days 1, 8, 15, carboplatin AUC 6 day 1 for every 3 weeks) before surgery, stratified by partial or no response (stable disease and progression of disease) evaluated by ultrasonography. Pathologic response of the primary tumor was assessed by using Miller and Payne grading system. We defined grade 4/5 as excellent response, grade 3/4/5 as response and treatment delay as paclitaxel administration being delayed at least 1 week because of toxicity in this study. 213 patients (2 cases with concurrent bilateral breast cancer) were eligible for analysis, 109 patients with 110 lesions in arm A and 104 patients with 105 lesions in arm B. Patients in arm B had a higher excellent pathologic response rate and a higher pathologic response rate compared with patients in arm A (59.0 vs. 45.5%, P = 0.046 and 86.7 vs. 71.8%, P = 0.007). Pathologic complete response (pCR) rate in breast alone was similar between two arms (P = 0.733), but there was a higher pCR rate in patients with partial response to two cycles of cyclophosphamide/pirarubicin/fluorouracil than those with no response (32.4 vs. 13.9%, P = 0.001). There was no treatment-related death, however more patients in arm B than in arm A experienced treatment delay caused by toxicity (60.6 vs. 11.9%, P < 0.001). Under the condition of same cumulative doses, weekly paclitaxel was more effective than 3 weeks schedule in terms of pathologic response to primary chemotherapy in breast cancer, and caused more treatment delay related to toxicity though well tolerant.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Breast Neoplasms; Carboplatin; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Staging; Paclitaxel; ROC Curve; Treatment Outcome

To investigate the clinical value of neoadjuvant chemotherapy in the treatment of operable breast cancer.. A total of 120 patients with pathologically proven operable breast cancer were randomized into two groups to receive 2-4 cycles of neoadjuvant chemotherapy with docetaxel combined with pirarubicin (TThp) or docetaxel combined with epirubicin (TE). Operations were performed two weeks after the neoadjuvant chemotherapy. The short-term therapeutic effect, toxic reaction and the impact of neoadjuvant chemotherapy on the choice of surgical approaches were evaluated.. The total effective rate for the primary sites was 87.2% in these patients, and the rate of breast conservation significantly increased from 12.7% to 41.8% (P<0.05), with a tumor resection rate of 97.2%. The major adverse effects of the therapy included leukopenia, nausea, vomiting and alopecia.. Neoadjuvant chemotherapy can enhance the breast conservation rate, lower the clinical staging of the tumors and minimize the surgery area to improve the postoperative quality of life of the patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Doxorubicin; Epirubicin; Female; Humans; Middle Aged; Neoadjuvant Therapy; Taxoids

Twenty-four eligible patients (23 of whom were evaluated) with advanced and metastatic breast cancer were treated at the Saitama Cancer Center every 4 weeks with pirarubicin (30 mg/m2 i.v., day 1 and 8), cyclophosphamide (200 mg/m2 div, day 1 and 8) and doxifluridine (800 mg/day po, day 1-14). The 23 evaluable patients had a median age of 49.7 years (range 35.3-72.1) and underwent a median number of 3 cycles (range 2-5). Grade 4 leukopenia (10/24 patients) was the dose-limiting factor and led to infection in one patient. Four complete responses and 7 partial responses with a median duration of 12.1 months (range 2.6-61.0) were achieved, resulting in an overall response rate of 47.8%. The 50% survival duration was 22.9 months.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Floxuridine; Humans; Leukopenia; Middle Aged; Neoplasm Recurrence, Local

We conducted a randomized controlled study to evaluate the clinical usefulness of (2"R) -4'-O-Tetrahydropyranyladriamycin (THP)-based combination therapy subsequent to induction therapy which was consisted with THP, 5'-DFUR, and CPA in the treatment of advanced or recurrent breast cancer. In maintenance therapy, Arm C received CPA and TAM, and Arm T received these two drugs plus THP. Survival time of 50% for all cases in which maintenance therapy was conducted was 26.9 months in Arm T and 20.9 months in Arm C, showing no significant difference by the log-rank test (p = 0.64). Survival time in all cases in which therapy had been completed was 54.6 months in Arm T and 28.1 months in Arm C, showing a significant difference by the log-rank test (p = 0.03) although the number of cases was few. A few cases showed a decrease in total leukocyte count to below 2,000/mm3 at the time of induction therapy, but this was transient in all cases. No significant difference in count was noted between two arms at the time of maintenance therapy. However, many cases in Arm T showed decreased total leukocyte count and hemoglobin content, and thrombocytopenia. These results suggest that combination therapy including THP conducted as maintenance therapy after induction is useful in the prolongation of survival time in patients with advanced or recurrent breast cancer.

Topics: Adult; Alopecia; Anorexia; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Floxuridine; Humans; Japan; Middle Aged; Nausea; Neoplasm Recurrence, Local; Survival Analysis; Vomiting

Improved quality of life has gained importance over shortly lasting remissions in yet incurable metastatic breast cancer. Fractionation of drug administration is one of the possible approaches to reduce the concentration-dependent toxicity of anthracyclines. We evaluated the pharmacokinetics of 4'-O-tetrahydropyranyladriamycin (THP-ADM) under weekly administration in patients with advanced breast cancer (dose escalation, from 20 to 27 mg/m2 THP-ADM). The concentration-time curves of THP-ADM in plasma were best described by an open three-compartment model [half-life of the first disposition phase (t1/2 alpha), 3.15 min; terminal elimination half-life (t1/2 gamma), 13.9 h] with a mean area under the curve (AUC) of 12.2 ng h ml-1mg-1 m-2, resulting in a mean plasma clearance of 86.9 1h-1 m-2. Metabolism included the formation of Adriamycin (ADM), Adriamycinol (ADM-OH), 13-dihydro-4'-O-tetrahydropyranyladriamycin (THP-OH), 7-deoxyadriamycinone (7H-ADn), and 7-deoxy-13-dihydroadriamycinone (7H-ADn-OH), with maximal plasma concentrations ranging from 2.8 to 5.5 ng/ml. The mean total amount of cytotoxic anthracyclines excreted into urine, mainly as the parent drug, was 5% of the delivered dose. ADM and ADM-OH, but not the parent drug, were observed in urine at up to 4 weeks after the last therapeutic cycle. There was a significant correlation between the leukocyte nadir under therapy and the AUC of ADM-OH (r = 0.800, P < 0.05). Since no shift in the plasma kinetics was observed from the first to the sixth cycle, the favorable ratio of the AUCs of THP-ADM and ADM after fractionation of THP-ADM suggests lower toxic side effects attributable to ADM. This hypothesis was confirmed in a clinical study, where no severe cardiotoxicity and only mild alopecia were observed in 19 patients. Thus, pharmacokinetics studies might be helpful in both individualization of therapy with THP-ADM and optimization of the administration schedule.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Humans; Middle Aged

Ideally, in preoperative intra-arterial infusion chemotherapy (regarding advanced breast cancer) is to obtain the most significant effects concerning histological features. Intra-arterial infusion chemotherapy using epirubicin (EPI), used in conjunction with daily doses of 1,200 mg medroxyprogesterone acetate (MPA), have recently been performed. This procedure has shown remarkable histological effects in the metastatic lymph nodes as well as in the primary lesions. These results were especially remarkable in the patients who were administered MPA (daily) two weeks prior to EPI infusion. These patients showed a complete disappearance of tumor cells. The results were interesting in view of the mechanism of action. Intra-arterial infusion chemotherapy combined with MPA may also be valuable in treating metastatic liver tumors and recurrent lesions in the regional lymph nodes such as supraclavicular tumors. A high response rate was obtained in the chemo-endocrine therapy when combined with MPA as a pretreatment. Thus, MPA may be expected to be available as a systemic therapy, too. In the future, a new development in the field of intra-arterial infusion chemotherapy may be achieved by utilizing a combination of angiogenesis inhibitors and peripheral blood stem cell transplantation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Epirubicin; Female; Humans; Infusions, Intra-Arterial; Lymphatic Metastasis; Medroxyprogesterone Acetate; Middle Aged; Neoplasm Recurrence, Local; Remission Induction

Doxorubicin containing combination chemotherapy regimens are widely used for treatment of breast and other cancers. However, these regimens are associated with significant toxicities including myocardial dysfunction and alopecia. Analogues of doxorubicin are being developed to reduce these side effects. We conducted a Phase II trial of an anthracycline analogue, pirarubicin, administered in combination with 5-fluorouracil and cyclophosphamide every 3 weeks, as front-line chemotherapy in women with metastatic breast cancer. Patients who had received prior anthracycline therapy were excluded. The chemotherapy doses were as follows: 5-fluorouracil (500 mg/m2 on days 1 and 8), pirarubicin (50 mg/m2 on day 1), and cyclophosphamide (500 mg/m2 on day 1). Among 40 evaluable patients treated on this protocol, a major response (partial or complete remission) was observed in 26 patients (response rate, 62%; 95% confidence interval, 46-77). The median response duration was 8 months, and median survival was 16 months. Grade III/IV myelosuppression occurred in 81% of the courses. The median cumulative pirarubicin dose was 410 (range, 90-870) mg/m2. A significant decrease in left ventricular ejection fraction occurred in 12 patients (at a median cumulative pirarubicin dose of 460 mg/m2) and led to congestive heart failure in 4 of these patients (cumulative pirarubicin doses of 500, 520, 590, and 730 mg/m2, respectively). Eleven patients underwent endomyocardial biopsy, either because they experienced a drop in left ventricular ejection fraction or because they had received a cumulative pirarubicin dose of 600 mg/m2 and were still responding to the treatment. Of these, only one biopsy was found to be more than grade 1.0 (in an individual who had received a cumulative dose of 705 mg/m2). Severe alopecia occurred in two-thirds of the patients. Pharmacokinetic studies revealed a triphasic elimination of pirarubicin with alpha, beta and gamma half-lives of 0.12, 1.44, and 33.9 h, respectively. Total clearance of drug was 4.2 liters.1 h/kg while the cumulative 24-h urinary excretion was less than 10% of the administered dose. The activity of the combination appears to be similar to doxorubicin-containing regimens, while the incidence of alopecia appears to be lower than the historical experience with doxorubicin. However, cardiotoxicity remains a significant problem.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Confidence Intervals; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Heart; Heart Failure; Humans; Incidence; Menopause; Middle Aged; Neoplasm Metastasis; Survival Analysis

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Nausea

Data of all phase II studies of pirarubicin (THP-doxorubicin) have been analysed for toxicity or activity in breast cancer and compared with published reports on doxorubicin, epirubicin or mitoxantrone used as single drugs. A graph of the 95% confidence intervals for each event was used. The results suggest that pirarubicin is as effective as other intercalating drugs in breast cancer and grossly better tolerated than doxorubicin, especially alopecia and cumulative cardiotoxicity. The equimyelotoxic doses of each drug were also estimated. The methodology and the validity of such historical comparisons is discussed: they cannot replace prospective randomised phase III studies, and do not allow definitive conclusions. However, most comparative trials of anticancer drug analogues cannot answer the right questions because their objectives are not adequate (especially for equiefficacy). But early evaluation by historical comparisons can help the conception of phase III studies.

Topics: Breast Neoplasms; Doxorubicin; Drug Evaluation; Epirubicin; Female; Humans; Mitoxantrone; Therapeutic Equivalency

Thirty elderly (over 70 years) women with measurable advanced breast cancer entered into this Phase II study. An initial dose of 30 mg/m2 of pirarubicin (THP) every 3 weeks was given intravenously. THP was escalated by levels of 10 mg/m2 according to the blood cell count done at day 14 and day 21 until a maximum dose per cycle of 70 mg/m2 was reached. The mean total cumulative dose of THP received was 204 mg/m2 (range 30-710 mg/m2). The mean number of cycles given was 5.5 (range 1-24). Of 28 evaluable patients, 1 achieved a complete response (CR), 6 had a partial response (PR) (CR + PR = 25%; 95% confidence interval 9-41%), 13 showed no change, and 5 had a progressive disease. The median time to progression was 3 months (range 0.5-18+ months). Of 28 patients evaluable for toxicity, the hematologic toxicity at day 15 was neutropenia grade 3 and 4 in 61% of the patients and thrombopenia grade 3 and 4, 0% of cycles. No cumulative hematologic toxicity was detected. Nonhematologic toxicities consisted of nausea and vomiting in 50% of patients (WHO grade 3 = 5%) and alopecia in 64% (WHO grade 2-3 = 36%). No stomatitis occurred. No cardiac toxicity was observed. The results of this study show that THP is an active drug in elderly patients with advanced breast cancer. Because of its safety, THP deserves further investigation in this application.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Humans; Remission Induction; Survival Analysis

A phase I-II study of weekly low-dose pirarubicin was performed in 19 patients with advanced breast cancer. The goal was to establish the optimal dose intensity, i.e., the maximal dose applicable at tolerable toxicity within the intended schedule. Each of the four different dose groups used (20, 24, 25, and 27 mg/m2) comprised 4-5 patients. In over 47% of patients, objective remissions were obtained (confidence interval 26%; 71%) including one complete and eight partial remissions; the median duration of remission was 41 weeks (range 16-72), and the median time to reach remission was 12 weeks (range 6-36). Efficacy of treatment was more dependent on prior chemotherapy than on pirarubicin dosage. The weekly i.v. push injection of the drug was easily applicable at an outpatient clinic and well tolerated. WHO grade 3 was the highest toxicity observed for leukopenia (3/19), leukopenia associated with infection (1/19), nausea/vomiting (2/19) and alopecia (6/19). More severe myelosuppression was avoided by interrupting the weekly application until recovery of leukocytes to greater than or equal to 3.5 x 10(3)/mm3. No clinical signs of cardiotoxicity were observed. Generally, mild to moderate signs of cardiac dysfunction acquired during therapy were detected by special cardiac monitoring. Only in 3 of 19 patients was a cumulative dose of more than 550 mg/m2 surpassed. This was accepted as the upper limit for conventional anthracycline therapy. The median cumulative dose applied was 325 mg/m2/week (range 58.2-800.0). Because of maldistribution of prognostic factors, no dose-response relationship could be established. With respect to the total time for which each patient was studied, the dose group of 27 mg/m2 achieved the highest dose intensity with a median of 17.4 mg/m2/week (range 13.5-22.4). Therefore, the dosage of 27 mg/m2/week is recommended to be used in further phase II-III trials of weekly applied pirarubicin.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Heart Diseases; Hematologic Diseases; Humans; Kidney Diseases; Middle Aged; Remission Induction

Pirarubicin is a more lipophilic derivative of doxorubicin, with a higher uptake rate of cells, lower cardiotoxicity and better antitumor efficacy in preclinical models. Thirty-four patients with metastatic breast cancer were treated in a multicenter phase II study with pirarubicin (THP) using a dosage of 75 mg/m2/every 3 weeks. The patients had a median age of 56 years (range 41-73) and a performance status of WHO grade 0-2. Patients pretreated with anthracyclines, or who were older than 75 years and without sufficient bone marrow reserve were excluded. The 32 evaluable patients received a median number of 4 cycles (range 2-8). The myelosuppression was dose-limiting and led to infections (grades 1 and 2) in 5 patients. Twenty-eight patients developed leukocytopenia grade 3 and 4 toxicity and 7 patients experienced thrombocytopenia grade 1 and 2. The drug was subjectively well tolerated and nausea, vomiting and alopecia were mild. One complete remission with a duration of 15.4 months (67 weeks) and 7 partial remissions with a median duration of 9.3 months (40 weeks) were achieved, which resulted in an overall response rate of 25%. Twenty-one patients were stable for 17 weeks (median) under the treatment with pirarubicin.

Topics: Adult; Aged; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Follow-Up Studies; Humans; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Survival Rate

4'-O-Tetrahydropyranyl adriamycin (THP adriamycin) is a new anthracycline active as a single drug in advanced breast cancer. We have undertaken a phase II study as first-line treatment for metastatic disease with THP adriamycin day 1 = 40 mg/m2 i.v. bolus and 5-fluorouracil day 1 to day 5 = 750 mg/m2 as a continuous i.v. infusion. The dose of THP adriamycin was further escalated up to the maximal tolerated dose defined as grade 3 granulopenia for each patient. Thirty-nine patients were included, 37 being so far evaluable for toxicity and for efficacy. The mean number of cycles given was 5 (range: 2-12). The overall response rate (CR + PR) was 54% (95% CI: 37.9-70.1) and the CR rate 8%. Sites of response were as follows: lung 6/9, liver 11/18, breast 4/8, nodes 7/14, skin 3/8, bone 2/8. Neutropenia with grade 3 + 4 nadir values was observed in 70.2% of the patients according to the objective of the study. No severe thrombopenia or anemia occurred. Stomatitis grade 3 was seen in 27% and grade 4 in 3% of the patients. Alopecia grade 2 was seen in 18% and grade 3 in 9%. No other toxicity was observed. We conclude that this association is effective in metastatic breast cancer, giving few alopecia. A high response rate in liver metastases warrants further evaluation.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Hematologic Diseases; Humans; Middle Aged

Previous clinical studies have suggested that 4'-O-tetrahydropyranyl-doxorubicin (THP) as well as 5-fluorouracil/high-dose folinic acid (5-FU/HDFA) are active and well-tolerated drugs in breast cancer treatment. This phase I-II study was designed to determine the maximum tolerated dose (MTD) of THP in combination with 5-FU/HDFA as a weekly schedule and to examine the activity and safety of this drug regimen in patients with advanced breast cancer. 5-FU and HDFA were set at doses of 350 mg/qm i.v. and 500 mg/qm i.v., respectively, whereas the THP dose has been escalated in increments of 5 mg/qm i.v. beginning at a dose level of 10 mg/qm until reaching of MTD in at least four patients in one dose level. For determination of MTD the first six cycles of each patient have been taken into account. Up to July 1990, 21 patients previously not treated with chemotherapy for metastatic breast cancer were entered into the study; the latest patient entered at 35 mg/qm THP dose level. A total of 270 cycles have been administered so far. Anemia and leukopenia was limited to ECOG grades I and II. Other toxicities were mild or moderate. No acute or subacute cardiotoxicity has been observed. Up to July 1990, MTD had not been reached. In the second part of the study, at least another 14 patients have to be entered in a dose level one below the MTD to evaluate the activity and safety of this regimen in a phase II trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Middle Aged

The chemotherapeutic treatment of advanced and recurrent breast cancer was examined in a randomized controlled comparison test. Group A received (2"R)-4'-O-tetrahydropyranyladriamycin (THP) in combination with 5-fluorouracil (5-FU) and cyclophosphamide (CPA), while Group B was administered adriamycin (ADR) together with 5-FU and CPA. These combined chemotherapies were administered in a dosage regimen that was repeated in a 28-d cycle. On d 1 and d 8, THP and ADR were given at a dose of 30 mg/m2 IV and 5-FU was administered at a dose of 500 mg/m2 IV. CPA was administered at a dose of 100 mg/body, PO on consecutive days from d 3 to d 16. Among 37 complete cases in Group A, a complete response (CR) was noted in one patient and a partial response (PR) in 12, to give a rate of 35.1%. CR was noted in one patient and PR was observed in 7 out of 27 complete cases in Group B, giving a response rate of 29.6%. The mean PR duration was 19 wk (range, 4+--63) in Group A, and 14 wk (range, 4+--51+) in Group B. The 50% survival duration was 20.6 mo and 14.3 mo in Groups A and B, respectively, while mean survival duration was 17.9 mo and 16.6 mo in Groups A and B, respectively. No significant between-group differences were found for any of these measures. There were fewer side effects in Group A than in Group B, with Group A showing significantly less alopecia (P less than 0.01) and a lower incidence of anorexia (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Japan; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Random Allocation

A comparative study of two combination chemotherapy regimens including (2'' R)-4'-O-Tetrahydropyranyladriamycin (THP) or Adriamycin (ADR) was performed to evaluate its efficacy and safety in advanced and recurrent breast cancer. In this study 64 patients were evaluated, and the response rate was 35.1% (13 of 37 patients) in group A (combination chemotherapy of THP, 5-Fluorouracil and cyclophosphamide), and 29.6% (8 of 27 patients) in group B (ADR, 5-Fluorouracil and cyclophosphamide). There was no statistically significant difference between the response rates of the two groups. As for safety, that of group A was significantly superior to group B for alopecia while that of group A tended to be lower than group B for anorexia. From the above results, THP in combination with cyclophosphamide and 5-Fluorouracil is comparable to ADR in efficacy and can be regarded as having better safety than ADR for the treatment of breast cancer.

Topics: Anorexia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Humans; Middle Aged; Nausea; Neoplasm Recurrence, Local; Random Allocation

The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Doxorubicin; Female; Humans; Liposomes; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Polyethylene Glycols

In this study the chemotherapeutic agent Pirarubicin (PRB) which is known for its serious side effects was actively targeted to the breast cancer cells by uploading it to the biocompatible and biodegradable Sterically Stabilized Micelles (SSMs) made of 1,2- Distearoyl- sn- glycero‑3- phosphoethanolamine- N- methoxy‑ polyethylene glycol 2000 (DSPE-PEG

Topics: Animals; Breast Neoplasms; Doxorubicin; Female; Humans; Mice; Mice, Nude; Micelles; Polyethylene Glycols; Vasoactive Intestinal Peptide

To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG. The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Carriers; Female; Humans; Mice; Mice, Inbred BALB C; Micelles; Polyethylene Glycols; Vinorelbine

To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM).. Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed.. By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant.. The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

Topics: Breast Neoplasms; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Female; Gelatin; Humans; Liver Neoplasms; Prognosis; Retrospective Studies

The incidence of pregnancy-associated breast cancer (PABC) is increasing nowadays, and its diagnosis and treatment remain complicated due to the consideration of the fetus. The available data on PABC are primarily derived from case reports since there are ethical restrictions on conducting randomized clinical trials. In the present work, we reported a case of the human epidermal growth factor receptor 2 (HER2)-positive PABC and described the diagnosis and treatment for such type of breast cancer.. A 27-year-old patient was admitted to our hospital with the complaints of right breast mass for 3 days, and she was a first-time pregnant woman with a single live intrauterine fetus at 26 + 3 weeks of gestation. Physical examination of the right breast revealed a palpable and hard mass with obscure boundaries (5.0 cm × 4.0 cm) in the upper outer quadrant. Significant axillary lymph nodes (2.0 cm) were also present.. PABC.. To protect the fetus, breast ultrasonography was used to test her breast mass, a core needle biopsy was adopted to confirm the diagnosis, and abdominal ultrasound and chest X-ray were used to evaluate the metastasis. The patient was scheduled for neoadjuvant therapy using bi-weekly pirarubicin in combination with cyclophosphamide (AC) without anti-HER2 therapy for consideration of the fetus's safety. After 4 cycles of AC, the patient delivered a healthy male infant. After the delivery, all the treatments were carried out according to the standard recommendation for HER2 + breast cancer as non-pregnant patients.. After the surgery, the disease-free survival for the patient was 12 months until brain metastasis was diagnosed. She was still undergoing second-line anti-HER2 therapy and currently in a stable situation. Besides, the child was also healthy so far.. The methods for the diagnosis and treatment of PABC that result in teratogenesis should be avoided to protect the fetus. Mammogram and chest X-ray were safe approaches for the fetus. Moreover, chemotherapy-based on pirarubicin in combination with cyclophosphamide had no risk to the fetus.

Topics: Adult; Antineoplastic Agents; Biopsy, Large-Core Needle; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Gestational Age; Humans; Mastectomy, Extended Radical; Neoplasm Staging; Postnatal Care; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Receptor, ErbB-2; Trastuzumab; Ultrasonography, Mammary

Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death. Subsequently, the cytotoxic T lymphocytes (CD3

Topics: Adjuvants, Pharmaceutic; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Immunity; Lipids; Male; Mice; Mice, Inbred BALB C; Nanostructures; Oligopeptides; Rats; Rats, Sprague-Dawley; T-Lymphocytes, Cytotoxic

Breast cancer is believed to result from the interplay of genetic and non-genetic risk factors, and individual genetic variation may influence the efficacy of chemotherapy. Here we conducted a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer patients. In the discovery stage, we divided 92 patients who received anthracycline-based neoadjuvant chemotherapy into 2 groups according to pathologic response and performed a genome-wide study using Affymetrix SNP6.0 genechip. Of 389,795 SNPs associated with pathologic complete response (pCR), we identified 2 SNPs, rs6044100 and rs1799937, that were significantly associated with pCR after neoadjuvant chemotherapy. In the validation stage, genotype analysis of samples from an independent cohort of 401 patients who received anthracycline-based neoadjuvant regimens and 467 patients who received taxane-based regimens was performed using sequencing analysis. We found that only SNP rs1799937, located in the WT1 gene, was associated with pCR after anthracycline-based neoadjuvant therapy (AA vs GG; odds ratio [OR], 2.81; 95% confidence interval [CI], 1.13-6.98; P < 0.05) but not after taxane-based neoadjuvant therapy (AA vs GG; OR, 0.85; 95% CI, 0.36-2.04; P = 0.72). These results suggest that WT1 may be a potential target of anthracycline-based neoadjuvant therapy for breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Case-Control Studies; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Genome-Wide Association Study; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Polymorphism, Genetic; Prognosis; Survival Rate; WT1 Proteins

The Asia-Pacific Breast Initiatives (APBI) I and II registries were established to collect safety data for patients with early stage breast cancer receiving adjuvant docetaxel-based regimens in the Asia-Pacific region.. Data from the two registries were combined to perform a safety analysis. Participants in the registry were women with early stage operable breast cancer with an intermediate or high risk of recurrence. These women received adjuvant chemotherapy that included docetaxel between 2006 and 2011. Adverse events (AEs) were recorded and analyzed.. Data were collected from 3,224 patients from 13 countries. The mean dose intensity of docetaxel was 24.1, 22.7, 25.1 mg/m2/week among patients receiving docetaxel-based monotherapy, combination therapy and sequential therapy, respectively. Granulocyte colony-stimulating factor (G-CSF) was given with docetaxel to 41.8% of women and 20.6% of women receiving prophylactic antibiotics. Adverse events were reported in 86% of patients (anthracycline-containing regimens vs. non-anthracycline regimens; 87% vs. 80%). The most common adverse events were alopecia, nausea, neutropenia, vomiting, and myalgia. Adverse events NCI CTCAE ≥Grade 3 were reported in 45.4% of patients. Serious adverse events were reported in 13% of patients, of which 2.5% led to study discontinuation. Forty-six deaths (1.4%) were reported, with no significant difference between regimens.. The safety parameters of adjuvant docetaxel therapy used to treat sequential Asian women were comparable to those reported in clinical trials evaluating the role of adjuvant docetaxel. No unusual adverse events linked to Asia-Pacific region patients were observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Docetaxel; Doxorubicin; Epirubicin; Female; Follow-Up Studies; Humans; Longitudinal Studies; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prospective Studies; Safety; Survival Rate; Taxoids; Young Adult

Different chemotherapy regimens may contribute differently to the development of Premature Ovarian Failure (POF) in women of reproductive age with breast cancer. Here we evaluated how two different chemotherapy regimens, CAF (tegafur + pirarubicin + ifosfamide) and DTC (docetaxel + pirarubicin + ifosfamide), affect the development of POF.. We enrolled 164 women of reproductive age with breast cancer (mean ± SD age of 34.56 ± 9.48 years). The patients were divided into two groups, which were respectively treated with CAF (n = 89) or DTC (n = 75) chemotherapy regimen. Both study groups were comparable in all analyzed characteristics at baseline. Patients were treated with respective chemotherapy regimen for 6 months and followed up for over 12 months after completion of chemotherapy. Study outcomes were occurrence rates of POF, menstrual status and recovery after completion of chemotherapy, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and oestradiol (E2).. At 6 months after completion of chemotherapy, POF incidence rates were significantly lower in the CAF group. Furthermore, the proportion of patients with eumenorrhea, menstrual disorders or chemotherapy-induced amenorrhea in this study group was also significantly different from the DTC group. Similarly, adverse changes of serum levels of FSH, LH and E2 were less pronounced in the CAF group.. Both tested chemotherapy regimens can cause POF; however, adverse effects of DCT chemotherapy regimen on ovarian function are more pronounced than those by CAF chemotherapy regimen.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Docetaxel; Doxorubicin; Estradiol; Female; Fluorouracil; Follicle Stimulating Hormone; Humans; Ifosfamide; Incidence; Luteinizing Hormone; Middle Aged; Primary Ovarian Insufficiency; Reproduction; Taxoids

This study examined the ability of amphiphilic poly(ethylene glycol) (PEG) derivatives to assemble into micelles for drug delivery. Linear PEG chains were modified on one end with hydrophobic vitamin E succinate (VES), and PEG and VES were mixed in different molar ratios to make amphiphiles, which were characterized in terms of critical micelle concentration (CMC), drug loading capacity (DLC), serum stability, tumor spheroid penetration and tumor targeting in vitro and in vivo. The amphiphile PEG5K-VES6 (PAMV6), which has a wheat-like structure, showed a CMC of 3.03 × 10(-6) M, good serum stability, and tumor accumulation. The model drug, pirarubicin (THP), could be efficiently loaded into PAMV6 micelles at a DLC of 24.81%. PAMV6/THP micelles were more effective than THP solution at inducing cell apoptosis and G2/M arrest in 4T1 cells. THP-loaded PAMV6 micelles also inhibited tumor growth much more than free THP in a syngeneic mouse model of breast cancer. PAMV6-based micellar systems show promise as nanocarriers for improved anticancer chemotherapy.

Topics: Animals; Antineoplastic Agents; Biological Transport; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Design; Humans; Hydrophobic and Hydrophilic Interactions; Intracellular Space; Mice; Micelles; Polyethylene Glycols; Spheroids, Cellular; Vitamin E; Xenograft Model Antitumor Assays

It has been reported that expression levels of DNA repair genes are frequently associated with chemotherapy sensitivity and prognosis in breast cancer (BC) subtypes. The poly (ADP-ribose) polymerase-1 (PARP1), one of the major DNA single-strand break (SSBs) repair proteins, has been demonstrated a role in BC development. Because many of the chemotherapeutic agents target the tumor cell DNA, a DNA damage repair protein function is expected to impact therapeutic responses. However, the predictive effect of PARP1 in neoadjuvant chemotherapy (NC) treated BC is still controversial. To investigate whether PARP1 expression in BC is a possible biomarker to predict chemotherapeutic response, we assessed PARP1 expression in BC specimens based on collagen gel droplet embedded culture-drug sensitivity test (CD-DST) (in vitro) results and chemotherapeutic response of NC (in vivo). The surgical specimens from 108 patients with BC were recruited for CD-DST and PARP1 immunohistochemistry. We found that higher nuclear PARP1 (nPARP1) expression correlated with increased in vitro chemosensitivity against docetaxel (p=0.001) and epirubicin (p=0.022) based on CD-DST results. We also found that tumors with high nPARP1 expression were more sensitive to anthracycline/taxane based chemotherapy and associated with pathologic responses to NC using univariate and multivariate analyses (p=0.019 and p=0.037, respectively). Taken together, we conclude that nuclear expression of PARP1 is a useful marker to predict BC therapeutic responses.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cyclophosphamide; Docetaxel; Doxorubicin; Drug Resistance, Neoplasm; Epirubicin; Female; Follow-Up Studies; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Logistic Models; Middle Aged; Neoadjuvant Therapy; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Retrospective Studies; Taxoids; Treatment Outcome

To assess the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast cancer patients after various neoadjuvant chemotherapies. Data from 138 locally advanced breast cancer patients with histological diagnoses were reviewed. Seventy patients (group 1) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 50 mg/m(2) pirarubicin every 21 days. Sixty-eight patients (group 2) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 75 mg/m(2) docetaxel every 21 days. The biomarker changes of the operated tumor tissues were compared with the initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%, 17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and 16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in group 2. There were significant differences between the groups regarding ER and Ki-67 status changes, and these changes can be used to inform treatment strategies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Cyclophosphamide; Docetaxel; Doxorubicin; Female; Humans; Ki-67 Antigen; Middle Aged; Neoadjuvant Therapy; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids

In our study, we aimed to develop a codelivery nanoparticulate system of pirarubicin (THP) and paclitaxel (PTX) (Co-AN) using human serum albumin to improve the therapeutic effect and reduce systemic toxicities. The prepared Co-AN demonstrated a narrow size distribution around 156.9 ± 3.2 nm (PDI = 0.16 ± 0.02) and high loading efficiency (87.91 ± 2.85% for THP and 80.20 ± 2.21% for PTX) with sustained release profiles. Significantly higher drug accumulation in tumors and decreased distribution in normal tissues were observed for Co-AN in xenograft 4T1 murine breast cancer bearing BALB/c mice. Cytotoxicity test against 4T1 cells in vitro and antitumor assay on 4T1 breast cancer in vivo demonstrated that the antitumor effect of Co-AN was superior to that of the single drug or free combination. Also, Co-AN induced increased apoptosis and G2/M cell cycle arrest against 4T1 cells compared to that of the single drug formulation. Remarkably, Co-AN exhibited significantly lower side effects regarding bone marrow suppression and organ and gastrointestinal toxicities. This human serum albumin-based codelivery system represents a promising platform for combination chemotherapy in breast cancers.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Breast Neoplasms; Carcinoma, Lewis Lung; Cell Cycle; Cell Proliferation; Doxorubicin; Drug Delivery Systems; Drug Therapy, Combination; Female; Flow Cytometry; Gastrointestinal Diseases; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles; Paclitaxel; Rats, Sprague-Dawley; Serum Albumin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Pirarubicin (THP) was conjugated onto the pendant carboxyl groups of poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) [PEG-b-P(LA-co-MCC)] through hydrazone, ester, and amide bonds, respectively, and the conjugates were assembled into micelles with diameters between 30 and 60 nm. The in vitro THP release of the three conjugate micelles was conducted in pH 7.4 and 5.0 buffer solutions, and conjugate micelles with hydrazone linkage had the fastest THP release rate. Their in vitro cytotoxicity was tested using mouse mammary adenocarcinoma EMT6 cells and in vivo anti-tumor activity in Balb/c mice models bearing EMT6 tumors were compared with free THP and with each other. The results showed that the polymer-THP conjugates displayed higher cell-uptakes and better anti-tumor activities than free THP at 4h, and among the three micelles, those with hydrazone linkage had the highest anti-tumor activity in vivo, while those with amide linkage were the lowest.

Topics: Adenocarcinoma; Amides; Animals; Antibiotics, Antineoplastic; Biological Transport; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Doxorubicin; Esters; Female; Hydrazones; Hydrogen-Ion Concentration; Kinetics; Mice; Mice, Inbred BALB C; Micelles; Particle Size; Polyesters; Polyethylene Glycols; Polymers; Propane; Solubility; Technology, Pharmaceutical

To evaluate the effect of anthracycline pirarubicin-based regimen in association with different ways of fluorouracil (5-Fu) as neoadjuvant and adjuvant chemotherapy for primary breast cancer.. Two hundred and eighty-nine primary breast cancer patients who were to be operated, two to eight cycles of pirarubicin in association with cyclophosphamide and 5-Fu (CTF or CTFci regimen) were given before operation. The pathological response rate, effect and its relation with the infusion routes of 5-Fu were analyzed.. The overall pathological complete remission (pCR) rate was 28.4%. The median follow-up period was 39 months. The 5-year DFS was 87.6% (95% CI:82.1% to 92.7%), 5-year DDFS was 89.9% (95% CI:84.0% to 95.8%), and overall survival was 99.6%. CTFci (5-Fu, continuous infusion) regimen was superior to CTF regimen in pCR rates (32.3% vs. 20.2%, P = 0.037), and 5-year DDFS were 92.9% and 80.1%, respectively (P = 0.015). The pCR group was superior to non-pCR group in 5-year DDFS (92.4% vs. 85.6%, P = 0. 033). The pCR rate of patients with ER/PR-positive tumor was significantly lower than those of ER/PR-negative (P = 0.004). The 5-year DDFS rates of HER-2 (+) and HER-2(-) groups were 75.0% and 91.9%, respectively (P = 0.043). In the ER/PR-positve group, the 5-year DDFS of CTFci regimen was superior to those of CTF regimen, 91.4% vs. 81.4% (P = 0.047).. CTF/CTFci regimen as neoadjuvant and adjuvant chemotherapy is effective for primary breast cancer. CTFci regimen is superior to CTF regimen in pathological complete response rate and 5-year DDFS. CTFci regimen may do better to ER/PR (+) patients' benefits compared with CTF regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Remission Induction; Retrospective Studies; Survival Rate

To compare the safety and efficacy of a combination of 5-Fu, pirarubicin and CTX (FPC) with FEC as a postoperative adjuvant chemotherapy for breast cancer.. A total of 655 breast cancer patients were treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1995-2005, 292 were treated with FPC (5-Fu 500 mg/m2 i.v. gtt on day 1, pirarubicin 40 mg/m2 i.v. on day 1, CTX 500 mg/m2 i.v. on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles); 363 with FEC (5-Fu 500 mg/m2 i.v. gtt on day 1, epirubicin 50 mg/m2 i.v. on day 1 and day 2, CTX 500 mg/m2 i.v. on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy.. Main side effects in both FPC and FEC groups were leukopenia and gastrointestinal toxicity, with a 5 year survival rate 88.7% in FPC and 85.7% in FEC group.. FPC regimen is safe with superior long-term survival rate when compared with FEC, thus could be recommended as a postoperative chemotherapy regimen for Chinese patients with breast cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Middle Aged; Survival Rate

A 53-year-old woman with left breast tumor was diagnosed as bilateral breast cancer(left; T3N3M0, Stage III C/right; T2N0M0, Stage II )in our hospital, both of which were revealed as invasive ductal carcinoma shown to be ER-negative, PgR negative and HER2-positive by core needle biopsy. In December 2004, paclitaxel and trastuzumab combination therapy was tried, but she went into shock just during administration of paclitaxel, and this therapy was discontinued. After that the triweekly CTF therapy was tried as an anthracycline containing regimen, and the lymph node metastases obtained a complete response after a month and a 38. 5% reduction of left primary breast tumor, which was the best response observed after three months. Time to progression was prolonged to 7 months(9 cycles). Although febrile neutropenia occurred in the first cycle, the therapy could be continued safely thereafter as an outpatient. Anthracycline-containing regimens are likely to be avoided because of the difficulty of combining with trastuzumab in the treatment of HER2 overexpressing advanced/metastatic breast cancer. But the CTF therapy of less cardiotoxicity and less alopecia, can expect longer use and better QOL as an alternative for HER2 overexpressing advanced/metastatic breast cancer patients.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Middle Aged; Paclitaxel; Receptor, ErbB-2; Shock

To evaluate the effects and toxicity of the neoadjuvant chemotherapy of docetaxel combined with epirubicin or pirarubicin on breast cancer, and to investigate the influencing factors of the response to neoadjuvant chemotherapy.. 160 patients with stage II/III breast cancer, all females, aged 47 (22-66), were treated with docetaxel plus epirubicin or pirarubicin with 3 weeks as a cycle. Two to six cycles of treatment were given before surgery. The clinical efficacy and toxicity of the treatment were evaluated, and the correlation between the influencing factors and the clinical parameters with treatment response was analyzed.. The clinical response rate (RR) was 90% (144/160), the complete response (CR) rate was 26% (41/160), the partial response (PR) rate was 64% (103/160). The stable disease (SD) rate was 8% (13/160). The progress disease (PD) rate was 2% (3/160), the pathologically complete remission (pCR) rate was 7% (11/160), and the tumor-pathological complete response (tpCR) rate was 2% (1.3/160). Univariate analysis showed that the tumor size, clinical stage, triple negative phenotype might be the meaningful parameters influencing the clinical response. The patients with smaller tumor size, low stage tumor, and being triple-negative were more likely to achieve CR (P = 0.0371, 0.0013, and 0.0019 respectively). Age, histological grading, ER/PR ratio, Her-2 status did not significantly influence the early response. Multivariate analysis showed that the disease stage might be the meaningful factors for better response (P = 0.0030). The major toxic reactions of the therapy included neutropenia, alopecia, nausea, and vomiting.. The combination neoadjuvant chemotherapy with docetaxel and epirubicin or pirarubicin is an effective method to treat breast cancer with tolerable toxicity. The meaningful parameter influencing the early response is clinical stage.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Doxorubicin; Epirubicin; Female; Humans; Logistic Models; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Taxoids; Young Adult

We report a case of good response to chemo-endocrine therapy with slight alopecia. A 55-year-old woman was diagnosed as advanced breast cancer with T4c, N3, M1, Stage IV, who was left cervical node-positive. She received 4 cycles of CTF (cyclophosphamide 100 mg/body/day 1-14, THP 30 mg/body/days 1,8, and 5-FU 750 mg/body/days 1, 8 4 wq) therapy in addition to oral tamoxifen (20 mg/body) administration. After this treatment, the primary tumor was markedly reduced (PR), and only slight alopecia was observed. Generally, 3 cycles of CAF (CEF) therapy induced severe alopecia (grade 3). But this CTF regimen caused grade 1 alopecia. Most women have strong resistance to alopecia. It seems that the quality of life for breast cancer patients was affected by the extent of the alopecia. Therefore, CTF therapy should be considered effective for advanced breast cancer patients while reducing the extent of alopecia.

Topics: Adenocarcinoma, Scirrhous; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Lymphatic Metastasis; Middle Aged; Quality of Life; Tamoxifen

To evaluate the feasibility and effect of fluorouracil (5-Fu) in association with anthracycline-based regimen as neoadjuvant chemotherapy for primary breast cancer.. For one hundred and eleven primary breast cancer patients with 114 lesions who were to be operated, two to six cycles of 5-Fu (continuous infusion) in association with epirubicin or pirarubicin and cyclophosphamide (CEFci or CTFci regimen) were given before operation. The response rate, side effect and its relation with tumor characteristics were studied.. The overall response rate was 87.7%, of which the complete clinical response was 39.5%, pathological complete response was 23.7%, only one patient (0.9%) showed progressive disease. The regimen containing pirarubicin was superior to epirubicin regimen in pathological complete response rate (P < 0.05). Alopecia was mild in pirarubicin regimen as compared with epirubicin regimen but neutropenia was more severe in pirarubicin regimen than that in epirubicin regimen. Hormonal receptor expressions were significantly related to treatment response, the pathological complete response rate was 33.3% in oestrogen or progestin receptor negative tumors, but it was 7.5% in the positive tumors (P < 0.005). No correlation was observed between treatment response and tumor size, as well as HER-2 expression.. CTFci/CEFci regimen as neoadjuvant chemotherapy is effective and safe for primary breast cancer. CTFci regimen is superior to CEFci regimen in response rate. The patients with negative hormonal receptor are more sensitive to the neoadjuvant chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Neoadjuvant Therapy; Neoplasm Staging; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome

The therapeutic efficacy of weekly coadministration of paclitaxel (TXL) and pirarubicin (THP) on docetaxel (TXT)- and epirubicin-resistant recurrent breast cancer, adverse reactions caused by this therapy, and the possibility of ambulatory treatment using it were evaluated. The present study was conducted in 11 patients with recurrent breast cancer with pretreatment with CEF and TXT. The site of recurrence was the lung in 9 patients, lymphnodes in 2, bones in 1, liver in 1 and local foci in 1. One cycle consisted of 20 mg/m2 of THP followed by 80 mg/m2 of TXL 4 h later, repeated three times every other week. Three to six cycles were conducted in each patient. An anti-emetic drug was administered before administration of THP as short premedication. Dexamethasone (16 mg; i.v.) and d-chlorpheniramine maleate (12 mg; p.o.) were administered 1 h before administration of TXL and ranitidine (100 mg; i.v.) was administered 30 min before administration of TXL. Ubidecarenone (30 mg/day; p.o.) was administered for 3 days. The response rate was 27.3% with a rating of PR in 3 patients, NC in 6, and PD in 2. Adverse reactions observed included transient facial hot flushes, alopecia grade 1 or milder grade 1 symptoms, and peripheral nerve damage. No adverse reactions such as myocardial disorders or congestive heart failure were noted. Grade 3 and grade 2 neutropenia occurred in 1 and 6 patients, respectively, and 4 patients were admitted for treatment of this. In conclusion, the short premedication was useful, and this was thought to make it possible to conduct ambulatory treatment with TXL + THP in some patients. The response rate of 27.3%, however, was not satisfactory. It will be necessary to clarify the characteristics of this therapy by administering it to a wider spectrum of patients.

Topics: Adult; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Paclitaxel

Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction chemotherapy for primary breast cancer. HER2 overexpression independently predicted response to neoadjuvant anthracycline-based chemotherapy. Patients with HER2-positive status are 4.54 times more likely to have a pathological complete response than those with negative status (p<0.005). HER2, ER and PR status were stable during treatment. P53 and Ki67 significantly increased after treatment (p<0.005 and p<0.0005). SBR grade, proliferation markers, ER evaluated before and after treatment predicted disease-free survival (DFS) in univariate analysis.

Topics: Aneuploidy; Antibiotics, Antineoplastic; Biopsy, Needle; Breast Neoplasms; Doxorubicin; Epirubicin; Female; Humans; Ki-67 Antigen; Lymphatic Metastasis; Menopause; Middle Aged; Mitosis; Neoplasm Staging; Predictive Value of Tests; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; S Phase; Treatment Outcome; Tumor Suppressor Protein p53

A 52-year-old female underwent radical mastectomy at the age of 41 for left breast cancer (n0, positive for ER). After a few years of adjuvant TAM therapy, follow-up was stopped at the age of 50 with no recurrence. She had suffered from symptoms of cold since January 2001 and came to our hospital complaining dyspnea on February 11. CXP showed pleural effusion of the entire thoracic cavity and she was admitted to the hospital immediately. Pleural exudate cytodiagnosis showed carcinomatous pleurisy; however, dyspnea and thoracic effusion were improved by continuous thoracic drainage and instillation therapy. Various examinations demonstrated that the carcinomatous pleurisy was due to recurrent breast cancer. They also showed local recurrence, left supraclavicular lymph node metastasis and multiple bone metastasis. Thus, combined chemoendocrine-therapy of CTF (CPA, THP and 5-FU) and anastrozole was administered. After 6 cycles of CTF, the carcinomatous pleurisy, local recurrence and left supraclavicular lymph node metastasis were diagnosed as CR by CXP, chest CT and US and multiple bone metastasis were diagnosed as PR by bone scintigram. The patient continues to be treated on an outpatient basis with no recurrence about one year after the beginning of the treatment (6 months after CTF 6 cycles) and she is taking anastrozole continuously.

Topics: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Medullary; Cyclophosphamide; Doxorubicin; Drainage; Drug Administration Schedule; Female; Fluorouracil; Humans; Lymphatic Metastasis; Mastectomy, Radical; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Pleural Effusion, Malignant; Pleurisy; Triazoles

We have investigated the usefulness of dual-isotope single photon emission computed tomography (SPECT) for predicting the response to chemotherapy in patients with breast cancer. Twenty-five patients with breast cancer were analyzed by SPECT using both 99m-technetium-tetrofosmin (99mTc-TF) and 201-thallium-chloride (201Tl). The relationship between response to chemotherapy and retention of each tracer was analyzed. 99mTc-TF retention was significantly higher in responders (42.0+/-37.9) than in non-responders (-11.3+/-34.6) (p=0.003). Ten of 13 patients (76.9%) with high 99mTc-TF retention (>15%) showed good response to chemotherapy, whereas 11 of 12 patients (91.7%) with low 99mTc-TF retention (<15%) did not respond to the therapy. The overall predictability to the response to chemotherapy was 84.0%. 201Tl retention (responders, 47.5+/-60.2% vs. non-responders, 55.8+/-45.0%; p=0.443) was not useful in therapeutic prediction, but was required to identify the lesion on the SPECT image. This is the first report to find that dual-isotope SPECT using 99mTc-TF and 201Tl is useful in predicting the response to chemotherapy in patients with breast cancer. Low 99mTc-TF retention is a strong predictor of therapeutic resistance, and high 99mTc-TF retention suggests a favorable response to chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radiopharmaceuticals; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

What should be the standard treatment for taxane-refractory metastatic breast cancer remains controversial. In this paper, a case in which the 5'-DFUR + CPA + THP therapy was effective for paclitaxel-refractory metastatic breast cancer is reported. A 41-year-old female received pectoral muscle preserved mastectomy under diagnosis of the left breast cancer in May 1996. In June, 1999, a coin lesion of 2.2 cm diameter was found in the left middle lung field with chest X-ray. Paclitaxel 210 mg/m2 (once for three weeks, 8 cycles in total) resulted in marked improvement. The regimen of paclitaxel 70 mg/m2 (medication consecutive once-weekly for three weeks, and withdrawal for next week; 1 cycle) was carried out continuously with the patient ambulatory. Because resistance to the treatment appeared at the time the total dose reached 2,700 mg, 5'-DFUR + CPA + THP therapy (THP 30 mg/m2 (i.v.) x day 1, CPA 77 mg/m2 (p.o.) x 14 days, 5'-DFUR 460 mg/m2 (p.o.) x 14 days; 3 weeks with 1 cycle) was carried out, and definite improvement in the lung findings were observed. 5'-DFUR + CPA + THP therapy may be of use as a second-line therapy in paclitaxel-refractory recurrent breast cancer.

Topics: Adult; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Floxuridine; Humans; Lung Neoplasms; Paclitaxel

We report a 35-year-old woman with locally advanced mucinous carcinoma of the breast with sudden growth acceleration. A pea-sized mass developed into an ulcerated large tumor within 1 month. After the combination of chemotherapy, radiation and hyperthermia, a radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps. Histological examination revealed a pure mucinous carcinoma with axillary lymph node involvement. Estrogen and progesterone receptors were not detected in the tumor. Twenty-five months after treatment, there is no sign of recurrent disease. Pure mucinous carcinoma generally has a less aggressive growth pattern as defined by tumor size, adherence to the overlying skin/bottom fasciae, estrogen and progesterone receptor positive and primary lymph axillary lymph node metastases. This case showed completely opposite features to all of these typical biological features of pure mucinous carcinomas.

Topics: Adenocarcinoma, Mucinous; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Disease Progression; Doxorubicin; Female; Humans; Mastectomy, Radical; Paclitaxel; Radiotherapy Dosage

We report a case of malignant pericardial effusion due to breast cancer that was successfully controlled by intrapericardial chemotherapy using pirarubicin. A 53-year-old woman underwent breast conserving therapy for left breast cancer in 1996. She was given CAF therapy and UFT as adjuvant therapy. Three years and 10 months after operation, she had malignant pericardial and pleural effusion. Pericardiocentesis and pleurocentesis were performed immediately. Pericardial effusion relapsed after some time and she was treated with intrapericardial chemotherapy using pirarubicin. After this treatment she has not suffered from pericardial effusion for 1 year and 4 months to date. This case suggests that intrapericardial chemotherapy is effective for malignant pericardial effusion.

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Breast Neoplasms; Doxorubicin; Female; Humans; Middle Aged; Pericardial Effusion; Pericardium; Pleural Effusion, Malignant

Juliano and Ling initially reported the expression of a 170 kDa glycoprotein in the membrane of Chinese hamster ovarian cells in 1976, and named this glycoprotein P-glycoprotein (P-gp) based on its predicted role of causing "permeability" of the cell membrane. After much research on anthracycline-resistance, this P-gp was finally characterized as a multidrug-resistant protein coded by the mdr1 gene. Multidrug resistance associated protein (MRP) was initially cloned from H69AR, a human small cell-lung carcinoma cell line which is resistant to doxorubicin (DXR) but does not express P-gp. MRP also excretes substrates through the cell membrane using energy from ATP catabolism. The substrate of MRP is conjugated with glutathione before active efflux from cell membrane. Recently, membrane transporter proteins were re-categorized as members of "ATP-Binding Cassette transporter"(ABC-transporter) superfamily, as shown at http://www.med.rug.nl/mdl/humanabc.htm and http://www.gene.ucl.ac.uk/nomenclature/genefamily/abc.html. A total of ABC transporters have been defined, and MDR1 and multidrug resistance associated protein 1 (MRP1) were reclassified as ABCB1 and ABCC1, respectively. Their associated superfamilies include 11 and 13 other protein, in addition to ABCB and ABCC, respectively. Lung resistance-related protein (LRP) is not a member of the superfamily of ABC transporter proteins, because it shows nuclear membrane expression and transports substrate between nucleus and cytoplasm. LRP was initially cloned from a non-small cell lung carcinoma cell line, SW1573/2R120 which is resistant to DXR, vincristine, etoposide and gramicidin D and does not express P-gp. The mechanisms of resistance remains unclear, and why some resistant cell lines express P-gp and others express MRP and/or LRP is likewise unclear.

Topics: Antibiotics, Antineoplastic; ATP-Binding Cassette Transporters; Biological Transport; Biopsy, Needle; Breast Neoplasms; Chi-Square Distribution; Culture Techniques; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Epirubicin; Female; Humans; Probability; Sensitivity and Specificity

We report a case of far advanced breast cancer showing an excellent response to chemo-endocrine therapy. A 40-year-old female with a huge ulcerated tumor on her left anterior chest visited our hospital. Distant metastases were found in the lymph nodes, liver and bone. Therefore, endocrine therapy (toremifene and medroxyprogesterone acetate) and chemotherapy (cyclophosphamide, Therarubicin and 5-fluorouracil) were started as a combination treatment. As a result, the main tumor and metastatic lesion were remarkably reduced, and extended mastectomy with resection of right axillary lymph nodes was performed. Histologically, cancer cells in the primary lesion mostly disappeared, and only one lymph node in the left axillary lesion showed metastasis. No recurrence was found for 16 months after the surgical treatment. The combined therapy in the present case was extremely effective.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Toremifene

A 25-year-old female with a large tumor on her left breast was examined at our hospital from August, 1999. Ipsilateral supraclavicular, infraclavicular and axillary lymph nodes were swollen. She was diagnosed as having locally advanced breast cancer of stage IIIb by fine needle aspiration cytology. After the administration of docetaxel (60 mg/m2/3 weeks x 3) failed to improve her condition, we changed the treatment to selective intra-arterial chemotherapy with THP-ADR (60 mg/body/day, day 1 & 8, 41 & 48) by Seldinger's method. The target vessels were the internal thoracic, lateral thoracic, thoracodorsal and deep cervical arteries. We also combined 5-FU 500 mg/body div and CPA 500 mg/body i.v. on the same days with intra-arterial chemotherapy. As a result, the main tumor and metastatic lymph node swelling was remarkably reduced (down-staging was obtained). No recurrence was found for 5 months after curative resection.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Cyclophosphamide; Docetaxel; Doxorubicin; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Paclitaxel; Taxoids

The case of a 49-year-old woman with axillary lymph nodes, multiple bone and multiple lung metastases from advanced breast cancer is reported. The patient responded remarkably to combination chemo- and endocrine-therapy. This patient was discharged after receiving 2 cycles of cyclophosphamide, pirarubicin and 5'-DFUR, while continuing to receive daily oral doses of 5'-DFUR and MPA. The patient experienced few adverse effects during chemotherapy. The patient enjoys an improved quality of life. This combined regimen has been confirmed to be an effective treatment for patients in advanced stages of breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Floxuridine; Fluorouracil; Humans; Medroxyprogesterone Acetate; Middle Aged

A 59-year-old female complaining of breast tumor with suppurative discharge was diagnosed as having advanced breast cancer (T4cN3M1-StIV), with giant liver metastasis. Seven courses of combined chemoendocrine therapy (CTF + MPA) were used. Following the chemoendocrine therapy, primary tumor, lung, pleural, supraclavicular and parasternal metastasis disappeared, and the liver metastasis was obviously diminished. These effects continued for 1 year 7 months. Although CTF + MPA chemoendocrine therapy is widely used with advanced or recurrent breast cancer, a clearly effective case has almost never been reported. The reason for the remarkable effect in this case was the consistent immunity to breast cancer.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Medroxyprogesterone Acetate; Middle Aged

Echocardiographic reports on 144 adults receiving anthracycline therapy and 18 controls were reviewed for the possible relationship between dosage and ejection fractions. The cardiotoxicity of each anthracycline drug was evaluated as follows: Pirarubicin = 0.8, Mitoxantrone = 3.4, Daunorubicin = 0.5, Aclarubicin = 0, and Epirubicin = 0.6 with Doxorubicin = 1 as a control. As a whole, the ejection fractions, which decreased subsequently compared with increasing amount of dosage, showed a remarkable decrease at the dosage level of 600 mg/m2. However, the ejection fractions differed among individual patients. It was predicted that heart failure would not develop when the ejection fractions exceeded 55%. It is desirable to stop anthracycline therapy when the ejection fractions drop to 55%.

Topics: Aclarubicin; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Breast Neoplasms; Daunorubicin; Doxorubicin; Echocardiography; Epirubicin; Female; Heart; Hematologic Diseases; Humans; Male; Middle Aged; Mitoxantrone; Radionuclide Imaging; Stroke Volume

A 66-year-old woman with locally advanced and metastatic breast carcinoma received combination chemotherapy, which comprised mitomycinC (total 84 mg) and anthracyclines (total : epirubicin 350 mg and pirarubicin 450 mg). She had been alive without tumor progression for more than one year thanks to these chemotherapies. Nevertheless, she thereafter complained of severe bone pain due to progression of bone disease. Since morphine administration could not give her sufficient pain relief, we tried to treat her bone pain with pamidronate in a dose of 30 mg weekly or biweekly. The pamidronate markedly relieved her bone pain and improved osteolytic bone lesions. In conclusion, pamidronate therapy can be a promising therapeutic modality for bone-derived pain in terminal patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Doxorubicin; Epirubicin; Female; Humans; Infusions, Intravenous; Mitomycin; Pamidronate

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Mastectomy; Middle Aged; Neutropenia; Pilot Projects; Thrombocytopenia; Treatment Outcome; Vinblastine; Vinorelbine

We treated 8 patients of Stage III and IV breast cancer preoperatively with THP-ADR intra-arterial infusion chemotherapy. The median dose was 200 mg with a range from 150 to 310 mg. The response rate of THP was 75.0% compared to 66.7% of ADR. Leucopenia was observed during THP treatment with a lower frequency of alopecia.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukopenia; Middle Aged; Preoperative Care

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Cefoperazone; Cisplatin; Doxorubicin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Ointments; Piperacillin; Radiation Injuries; Radiotherapy; Rectal Neoplasms; Sulbactam; Suppuration; Ulcer

A 53-year-old female with peritoneal metastasis of breast cancer was treated with hyperthermia with chemotherapy. One course consisted of THP 60 mg and FT 400 mg/iv (day 1), CPM 100 mg and MPA 800 mg/daily/po) with RF heating of hyperthermia monthly. After completion of 10 courses of this regimen, ascites completely disappeared and peritoneal metastases were not found observed in any peritoneal cavity with abdominal CT and ultrasound. Peritoneal metastasis of breast cancer was one of the worst reactions with any therapy. The patient has been living for about four years without any signs of recurrence, with the tumor markers within the normal range after surgery. Thermochemotherapy seems a very promising treatment modality for peritoneal metastasis of breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Hyperthermia, Induced; Lymphatic Metastasis; Middle Aged; Penicillin V; Peritoneal Neoplasms; Tegafur

Arterial infusion therapy with anticancer drugs is now attracting attention as a valuable modality for locally advanced breast cancer. Since 1977, we have used this therapy in 122 patients with primary breast cancer. The present report mainly discusses the clinical and histological response as well as the prognosis. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR, 4'-epi-ADR and THP-ADR were jointly or individually made in each artery. Clinical response, defined as CR + PR, was noted in 48.4% of 5-FU group and 72.7% of ADR-MMC group. Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 45.2% of main tumors and 25.4% of metastatic lymph nodes in the 5-FU group, and 70.9% main tumors and 46.3% of metastatic lymph nodes in the ADR-MMC group. The non-infusion group contained 27.7% of stage IIIb, against 72.2% in the infusion group. The 5-year overall survival rates were non-infusion group 62%, 5-FU group 34.1% and ADR-MMC group 66.2%. A significant difference was seen between the 5-FU infusion group and the ADR-MMC group (p = 0.03). Administration of high dose medroxy progesterone acetate for two weeks and 4'-epi-ADR infusion chemotherapy resulted in an excellent histological response. This combination therapy is a promising neoadjuvant chemo-endocrine therapy for advanced breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Doxorubicin; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Lymphatic Metastasis; Mitomycin; Prognosis

A 67-year-old advanced breast cancer patient with multiple bone metastases showed a remarkable response to the combination therapy of mitoxantrone (MIT) and medroxyprogesteron acetate (MPA) after failure of anthracycline therapy. Eight course of CTF (cyclophosphamide, THP-adriamycin, 5-fluorouracil) and subsequent 4'-epi-adriamycin were performed for locally advanced breast cancer and multiple bone metastases, but the ulcerated breast cancer enlarged. Then the combination therapy of MIT (10 mg/day) and MPA (1,200 mg/day) was carried out. Seven months after treatment, the ulcerated breast cancer disappeared completely and the serum levels of CA 15-3, TPA and CEA decreased within the normal range. These results suggest that combination therapy with mitoxantrone may well be effective against the anthracycline-resistant breast cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Doxorubicin; Drug Administration Schedule; Drug Resistance; Female; Humans; Medroxyprogesterone Acetate; Mitoxantrone

Topics: Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Doxorubicin; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Recurrence, Local; Outpatients; Tamoxifen; Treatment Outcome

A 55-year-old female was admitted for right breast tumor with multiple bilateral lung metastases. Modified radical mastectomy (Auchincloss method) was carried out. And the combination chemoendocrine therapy was undertaken using CPA 100 mg p.o. days 1-18, THP 40 mg i.v. days 1, 8, 5-FU 500 mg i.v. days 1, 8 and MPA 1,200 mg p.o. daily. One month later, the lung metastases completely disappeared on chest CT gram. Nine courses of chemotherapy with the same drugs were undertaken intravenously every four weeks. This therapy has been continuously effective for one and half years now. These results suggested the importance of a severe adjuvant therapy for the initial phase of advanced breast cancer.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Lung Neoplasms; Mastectomy, Modified Radical; Medroxyprogesterone; Middle Aged; Remission Induction

We evaluated the pharmacokinetics of pirarubicin during 16 courses of therapy in 4 patients suffering from breast cancer who were treated with an association of pirarubicin (30-60 mg/m2 according to the hematologic tolerance to the previous course, the first course being given at a dose of 40 mg/m2) and continuous infusions of 5-fluorouracil (750 mg/m2 daily for 5 days). Pirarubicin's pharmacokinetics and metabolism were linear within this dose range; the metabolites identified were pirarubicinol, doxorubicin and doxorubicinol (AUC ratios of metabolite/pirarubicin were 0.6, 0.64 and 0.57 respectively). Pirarubicin's decay from plasma followed a two-compartmental pattern, showing half-lives of 15.6 min and 16.6 h; the total plasma clearance of the drug was 140 l/h-1/m-2, and the total volume of distribution was 2,830 l/m2. A relationship was observed between some pharmacokinetic parameters and the toxic effects of the drug: the percentage of survival of granulocytes was significantly correlated with the AUC values for doxorubicin and doxorubicinol, whereas that of platelets was significantly correlated with the AUC values for pirarubicin and pirarubicinol. This is the first study to demonstrate a pharmacokinetic/pharmacodynamic relationship for pirarubicin.

Topics: Antibiotics, Antineoplastic; Blood Cells; Breast Neoplasms; Dose-Response Relationship, Drug; Doxorubicin; Drug Evaluation; Female; Half-Life; Humans; Time Factors

Intra-arterial infusion chemotherapy through a catheter incubated at the recurrent radial artery and connected to an implantable reservoir was performed in eight patients with supraclavicular lymph node metastasis including four locally advanced recurrent breast cancers and two inflammatory breast cancer. Clinical response in breast cancer patients was 1 CR, 3 PR, 1 NC, and 1 PD. There was no complication related with catheter insertion. Therefore from the aspect of quality of life, this system was considered useful for treatment of advanced breast cancer, especially locally advanced recurrent breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Catheterization; Doxorubicin; Female; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local

Between January 1977 and December 1989, 140 patients of Stage III breast cancer were treated in Sapporo Medical College. Sixty-six of these patients received intra-arterial infusion chemotherapy. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of ADR, MMC, 4'-epi-ADR or THP-ADR were jointly or individually made in each artery. The 5-and 10-year overall survival rates were: infusion group 49.2% and 49.2%, non-infusion group 64.0% and 45.0%, respectively. Intra-arterial infusion chemotherapy seems to be useful because non-infusion group contained mostly Stage IIIa and conversely the infusion group contained mostly Stage IIIb. A significant difference was seen between 5-FU infusion group and MMC.ADR group (p=0.026). MMC group, MMC + ADR combination group and 4'-epi-ADR group were marginally significantly different in terms of survival rates of the anticancer drugs of Stage IIIb.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Mitomycin; Mitomycins; Neoplasm Staging; Survival Rate

79 patients with advanced breast cancer were given Pirarubicin 20-25 mg/m2 during 3 consecutive days every 3 or 4 weeks. 78 were evaluable for response (41 without previous chemotherapy and 37 with only one previous regimen). The overall response rate was 35% (95% CI 24-45) and the complete response rate was 8%. In previously untreated patients, the response rate reached 41.5%. The limiting toxicity was a non-cumulative granulocystopenia, sometimes severe at these high doses, with a prompt recovery. The non-haematological toxicities were mild, and included 13% with grade 3 alopecia.

Topics: Adult; Aged; Agranulocytosis; Alopecia; Antineoplastic Agents; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Heart; Humans; Middle Aged

The efficacy and toxicity of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP) were assessed in the treatment of patients with advanced breast cancer by the Japan THP Study Group. Mean plasma levels of THP after single-dose administration revealed triexponential decay characterized by an initial half-life of 0.89 h. A higher concentration of THP was obtained in the metastatic lymph nodes than in the breast cancer tissue at 4 h after administration (4.01 vs. 1.17 micrograms/g). Whereas 1 complete (CR) and 12 partial response (PR) were observed in 56 evaluable patients after administration of THP alone (23.2%), 1 CR and 12 PR were observed in 37 evaluable patients who had combination therapy including THP (35.1%). Multivariate analysis of prognostic factor revealed that the site of metastases had the most valuable prognostic significance; second was irradiation in the previous treatment, and third was the disease-free interval. Life-table analysis adjusted with the Cox proportional hazard model revealed a similar survival curve of patients receiving THP-cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) to that of those receiving CAF only in spite of the low incidence of toxicity in the THP therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; In Vitro Techniques; Lymphatic Metastasis; Middle Aged

Pirarubicin is an anthracycline with broad antitumor activity, and without significant cardiotoxicity in preclinical and early clinical trials. We treated 40 evaluable patients with metastatic breast cancer and no prior exposure to chemotherapy with 5-fluorouracil, pirarubicin, and cyclophosphamide at 21-day intervals until reaching cumulative doses of 800 mg/m2 of pirarubicin, or the development of progressive disease. The median age was 56 years and the median performance status, 1. Seventeen patients had prior hormone therapy and 12 had prior radiotherapy. The median number of metastatic sites was three, with 11 patients having less than three sites. Twelve patients were premenopausal. The median disease-free interval was 6 months. Four patients achieved a complete remission and 21 a partial remission, for an overall response rate of 63%. The median response duration was 8 months and the median time to progression for all patients was 9 months. The median survival has not been reached, but will exceed 13 months. Gastrointestinal toxicity was minimal to moderate, whereas myelosuppression was severe. Complete hair loss was observed by only 58% of patients. There were two episodes of mild congestive heart failure at high cumulative doses of pirarubicin; both were controlled with medical treatment. This three-drug combination containing pirarubicin is effective in treating metastatic breast cancer, with less severe toxicity than other anthracycline-containing combinations.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Heart Diseases; Hematologic Diseases; Humans; Middle Aged; Remission Induction

THP-adriamycin (pirarubicin) is a new anthracycline-analogue. In France, the drug is achieving the phase II studies and the step of phase III studies is going on. As this point of its development, it is already possible to conclude that the drug probably shares the same efficacy as adriamycine, especially in breast cancer, but exhibits a better tolerance in term of alopecia and cardiac toxicity, as predicted by preclinical studies. Its pharmacological properties make the drug an original compound, exciting for investigations in the field of loco-regional therapy.

Topics: Alopecia; Antineoplastic Agents; Breast Neoplasms; Doxorubicin; Drug Tolerance; France; Heart Failure; Humans

Fourteen patients with metastatic breast cancer previously treated with one chemotherapy regimen received Pirarubicin at a dose of 70 mg/m2 at 3-week intervals. In 7 patients the dose had to be reduced, in 1 patient to 40 mg/m2 and in 6 patients to 50-60 mg/m2. There were 1 complete and 2 partial remissions. These objective responses were observed in soft tissue, lung and pleural areas and lasted 1+; 4+ and 5+ months. Grade 3 and 4 leukopenia was found in 42%, grade 3 thrombocytopenia in 2%, grade 3 nausea/vomiting in 29% of the cycles. Grade 1 and 2 alopecia occurred in 64% of the patients, the remaining 36% of the patients did not suffer from any alopecia. No cardiotoxic side effects were observed in 13 patients. In 1 patient with severe coronary heart disease extrasystoles and reduction in left ventricular ejection fraction occurred. Pirarubicin has antitumor activity in previously treated metastatic breast cancer patients.

Topics: Adult; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Humans; Middle Aged; Neoplasm Metastasis

In a phase II study, 35 patients with advanced breast cancer were treated with 4'-O-tetrahydropyranyl-doxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3-15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%-75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21 - 77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III-IV) and thrombocytopenia (9 patients, WHO grade II-IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II-III. Other treatment-related side effects included alopecia (WHO grade II-III) in 26 patients and stomatitis and diarrhea (WHO grade I-III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700-1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.

Topics: Adult; Aged; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Humans; Leukocyte Count; Leukopenia; Male; Middle Aged; Platelet Count; Survival Analysis

In a phase II study, 77 patients with metastatic breast cancer were treated with pirarubicin, 70 mg/m2 iv every 3 weeks. Most of them had received prior hormonal (n = 39) and/or chemotherapeutic drug treatment for advanced disease, including anthracycline-containing regimens in 17. After a median of 5.5 treatment cycles (range 1-14), objective tumor response was seen in 22/71 (31%) evaluable patients (4CR, 18 PR). Stable disease occurred in 34 (48%) patients, whereas the tumor progressed in 15 (21%). Significant hematologic toxicity (WHO grade III-IV) requiring interval and/or dose adjustments was observed in 41 (58%) patients. Other treatment-related side effects were generally mild, and included alopecia in 52 (73%), nausea and/or emesis in 50 (70%), and stomatitis and diarrhea in 3 patients each. There was no treatment-related death, nor was there any evidence of cardiac toxicity thus far. In summary, the early results of this trial suggest that pirarubicin is an active and rather well tolerated drug in pretreated patients with advanced breast cancer.

Topics: Adult; Aged; Alopecia; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Menopause; Middle Aged; Nausea; Vomiting

In 34 patients with primary advanced breast cancer, intra-arterial administration of ADR (50 mg X 3, total dose 150 mg, 10 cases), 4' epi ADR (50 mg X 3, 150 mg, 8 cases; 70 mg X 3, 210 mg, 10 cases) and THP-ADR (50 mg X 3, 150 mg, 6 cases) was performed, and its effects and side effect were analyzed. The clinical and histological response rate were superior in the ADR (150 mg) regimen and 4'-epi-ADR (150 mg) regimen. Signs of systemic toxicity such as gastrointestinal disorders, leukocytopenia and thrombocytopenia were the side effects in patients treated with THP-ADR, but the frequency of alopecia was lower. No cardiotoxicity was recorded in any of the patients. These results indicated that 4'-epi-ADR given the total dose of 150 mg in a single dosage of 50 mg was the most effective agent in intra-arterial infusion chemotherapy for advanced breast cancer.

Topics: Alopecia; Antineoplastic Agents; Breast Neoplasms; Doxorubicin; Epirubicin; Female; Humans; Infusions, Intra-Arterial; Leukopenia; Lymphatic Metastasis; Remission Induction; Thrombocytopenia

The clinical pharmacology and toxicity of a novel anthracycline derivative, 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), was investigated in patients with advanced malignant diseases. The starting dose was 30 mg/m2 which was escalated by increments of 10 mg/m2. Twelve patients with a median age of 42 (range, 19-69) years and a median Eastern Cooperative Oncology Group performance score of 2 (range, 1-2) were entered into the study. The diagnoses included four testicular cancers, two breast cancers, two small cell lung cancers, two acute myeloid leukemias, one colon cancer, and one hemangiosarcoma. THP-adriamycin was given as an i.v. bolus injection every 3 weeks. Evaluable were 18 courses for general toxicity, 16 courses for hematological toxicity, and 16 courses for pharmacokinetics. THP-adriamycin had a short initial half-life of 1.4 +/- 0.3 min (mean +/- SD) due to rapid cellular uptake. Peak concentrations in unseparated blood cells were reached 5 min after drug injection and remained higher than in plasma throughout the observation period of 72 h. The half-lives of THP-adriamycin in plasma were 19 +/- 2.8 min in an intermediate and 13 +/- 1.6 h in the terminal phase. A linear correlation was observed between the dose and the areas under the concentration curves for THP-adriamycin in plasma (r2 = 0.97) and blood cells (r2 = 0.99). The volume of distribution was 2124 +/- 221 liters/m2 and the total clearance rate 115 +/- 11 liters/m2h. THP-adriamycin was metabolized to Adriamycin, THP-adriamycinol, and adriamycinol. The major metabolite was Adriamycin with a terminal half-life in plasma of 33 +/- 10 h. The area under the curve of Adriamycin was also correlated to the administered dose (r2 = 0.96). Since excessive peak concentrations of Adriamycin were avoided, the treatment with THP-adriamycin might be an alternative to continuous infusions or weekly administrations. The maximum tolerated dose was 70 mg/m2, and the dose-limiting toxicities were leukopenia and thrombocytopenia. Anemia, nausea, and vomiting were mild to moderate, and no other toxicity was observed. All side effects were dose dependent and reversible. In a patient with breast cancer, a disease stabilization was achieved lasting for 9 weeks. No objective remission was observed. We suggest 60 mg/m2 in pretreated or poor risk and 70 mg/m2 in untreated or good risk patients every 3 weeks for further clinical trials.

Topics: Adult; Aged; Breast Neoplasms; Dose-Response Relationship, Drug; Doxorubicin; Drug Stability; Female; Humans; Kinetics; Male; Middle Aged; Temperature

THP-ADM is a new anthracycline with broad antitumor activity without cardiac toxicity or alopecia in experimental models. Phase I studies had established a proposed dose for phase II trials of 50 mg/m2 every three weeks. This modality gave an insignificant result in breast carcinoma. Cellular pharmacokinetics suggested that a longer time of administration could be more efficient. In this phase II trial oriented to advanced breast cancer, we have used 3 consecutive daily doses of 20 mg/m2/day in monthly cycles with dose escalation in each patient. We have observed 28% partial remissions (PR). Two patients previously treated with adriamycin had PR. Significantly less alopecia and no cardiac toxicity were observed.

Topics: Adult; Aged; Blood Cell Count; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Heart Diseases; Humans; Middle Aged; Neoplasm Metastasis

In a phase II study of THP, fifty-six patients with advanced or recurrent breast cancer were evaluated, and a response rate of 23.2% including 1.8% with complete response and 21.4% with partial response, was obtained. Response rates of THP varied according to the location of metastasis and the highest rate was shown to be 38.5% in patients with soft tissue metastasis. The median dose for inducing response was 100 mg with a range from 60 mg to 160 mg. Toxicities such as leukopenia and gastrointestinal disorders were observed during THP treatment. The favorable response to THP was close to that of adriamycin, but it was noteworthy that a lower frequency of alopecia occurred.

Topics: Adult; Aged; Anorexia; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Middle Aged; Nausea; Neoplasm Recurrence, Local

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Topics: Aged; Anorexia; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukopenia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Nausea; Neoplasms; Stomach Neoplasms; Thrombocytopenia

To investigate the detailed acute cardiotoxicity of the anthracycline antibiotics, adriamycin (ADM) and a tetrahydropyranyl derivative (THP-ADM), Holter ECG was recorded and some of the electrocardiographic parameters were analyzed. The basic rhythm was sinus rhythm in many cases except only one case which developed intermittent atrial fibrillation after the administration of ADM. No effect on the specialized conduction system was observed in either ADM or TH-PADM. In relation to the supraventricular premature beat, no increase of the pre-existing supraventricular extrasystole and fresh appearance of the supraventricular extrasystole were observed after the administration of these drugs. On the other hand, the ventricular premature beat was tended to increase after ADM administration, and the mode of appearance of the ventricular extrasystole was very dangerous and life-threatening. For example, short-run type and R on T type ventricular extrasystole were recorded. THP-ADM induced no significant increase of the ventricular extrasystole. The developed ST-T changes were seen after the administration of these drugs, but the patients complained neither the symptoms of heart failure nor stenocardia. In conclusion. THP-ADM had less cardiotoxicity than ADM.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Breast Neoplasms; Cardiac Complexes, Premature; Doxorubicin; Electrocardiography; Female; Heart; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms

The therapeutic effects of 4'-Epi-Adriamycin (Epi-ADR), THP-Adriamycin (THP-ADR) and Mitoxantrone on 30 patients with advanced and recurrent breast cancer were analyzed. Responders for Epi-ADR, THP-ADR and Mitoxantrone were 5/18, 3/8 and 2/8 respectively. Leukocytopenia less than 3000 was observed in 7/12 for Epi-ADR, 8/8 for THP-ADR and 7/8 for Mitoxantrone. Thrombocytopenia was found in 2 cases treated with Epi-ADR. Gastrointestinal disorders were observed in patients treated with Epi-ADR extensively with THP-ADR moderately and with Mitoxantrone slightly. Marked alopecia was remarkably seen in the patients treated with Epi-ADR, but it was only slight in those treated with THP-ADR and Mitoxantrone. No cardiotoxicity was recorded in any of the patients.

Topics: Adult; Aged; Alopecia; Anthraquinones; Breast Neoplasms; Doxorubicin; Epirubicin; Female; Humans; Middle Aged; Mitoxantrone; Nausea; Neoplasm Recurrence, Local; Vomiting

A phase II clinical trial of a new anthracycline, 4'-O-tetrahydropyranyladriamycin (THP-ADM), was performed in thirty-one patients with advanced malignant tumors refractory to standard chemotherapies. The dosage of THP-ADM was 40 mg/m2 by iv bolus injection repeated every 3 weeks. Of 3 evaluable patients with non-Hodgkin's lymphoma, one achieved partial remission. A minor response was noted in one out of 7 patients with gastric cancer and one out of 5 patients with ovarian cancer. Leukopenia less than 4 X 10(3)/cmm and thrombocytopenia less than 100 X 10(3)/cmm were seen in 81% and 19% of cases, respectively. Mild gastrointestinal toxicities including nausea and vomiting and anorexia were observed in about one third of the patients. Mild hair loss occurred in 2 patients (6%). No ECG abnormalities on clinical sign of cardiotoxicity were seen.

Topics: Aged; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Lymphoma; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Stomach Neoplasms