K. Aogi

Dofequidar Fumarate (MS-209) in Combination With Cyclophosphamide, Doxorubicin, and Fluorouracil for Patients With Advanced or Recurrent Breast Cancer

PURPOSE To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide, doxorubicin, and fluorouracil (CAF) therapy in comparison with CAF alone, in patients with advanced or recurrent breast cancer. Dofequidar is a novel, orally active quinoline derivative that reverses multidrug resistance. PATIENTS AND METHODS In this randomized, double-blind, placebo-controlled trial, patients were treated with six cycles of CAF therapy: 28 days/cycle, with doxorubicin (25 mg/m2) and fluorouracil (500 mg/m2) administered on days 1 and 8 and cyclophosphamide (100 mg orally [PO]) administered on day 1 through 14. Patients received dofequidar (900 mg PO) 30 minutes before each dose of doxorubicin. Primary end point was overall response rate (ORR; partial or complete response). In total, 221 patients were assessable. RESULTS ORR was 42.6% for CAF compared with 53.1% for dofequidar + CAF, a 24.6% relative improvement and 10.5% absolute increase (P = .077). There was a trend for prolonged progression-free survival (PFS; median 241 days for CAF v 366 days for dofequidar + CAF; P = .145). In retrospectively defined subgroups, significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal, had no prior therapy, and were stage IV at diagnosis with an intact primary tumor. Except for neutropenia and leukopenia, there was no statistically significant excess of grade 3/4 adverse events compared with CAF. Treatment with dofequidar did not affect the plasma concentration of doxorubicin. CONCLUSION Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy.

Factors Associated with Health-related Quality-of-life in Breast Cancer Survivors: Influence of the Type of Surgery

OBJECTIVE To determine if health-related quality-of-life (QOL) differences existed between breast cancer (BC) survivors receiving mastectomy and those receiving breast-conserving treatment (BCT). Factors associated with QOL in long-term BC survivors were also identified. METHODS One hundred patients who had previously undergone BC surgery and were alive without recurrence for >5 years were asked to answer the patient-administered questionnaires to assess their QOL (Functional Assessment of Cancer Therapy scale-Breast: FACT-B) and psychological distress (Hospital Anxiety and Depression Scale: HADS). Of them, 93 responded to the questionnaires affirmatively. RESULTS Although none of the QOL scores were related to the surgical procedures, statistically significant relationships were found between age and the scores of FACT-General and social/family well-being (SWB), and between the educational status and scores of SWB in univariate analyses. There was no statistically significant relationship between psychological distress and each factor examined. In multivariate analyses, significant correlations were established between scores of the FACT-BC subscale (FACT-BCS) and the type of surgery and between those on the FACT SWB subscale and age at study or educational status. Namely, patients who had undergone BCT, younger patients and patients with higher educational background scored higher QOL. CONCLUSIONS Among the BC survivors, those who underwent BCT experienced significantly but slightly better QOL than those who received mastectomy in FACT-BCS assessments. Younger patients and patients with higher educational backgrounds experienced significantly better SWB.

A feasibility study of psychosocial group intervention for breast cancer patients with first recurrence

Goals of workThe effects of psychosocial group interventions on improving quality of life (QOL) for patients with recurrent breast cancer are not well known. The objective of this study was to assess the feasibility of a psychosocial group intervention in Japanese women with first recurrence of breast cancer.Patients and methodThe subjects were consecutively selected from among patients who were diagnosed with a first recurrence of breast cancer. We conducted a 6-week psychosocial group intervention. QOL was assessed using the Profile of Mood States (POMS), the Impact of Event Scale—Revised, the Mental Adjustment to Cancer (MAC) scale, and the European Organization for Research and the Treatment of Cancer (EORTC) Quality of Life Questionnaire—Cancer 30/Breast module 23 (QLQ-C30/Br23) at baseline then immediately and 3 and 6 months after completion of the intervention.ResultsAmong 58 eligible patients, written consent was obtained from 28 (48%), and the final evaluation was conducted on 19 subjects. The repeated measured analysis of variance (ANOVA) revealed a significant change in tension–anxiety, depression–dejection, anger–hostility and total mood disturbance on the POMS, helplessness/hopelessness on the MAC scale, and body image and future perspective on the QLQ-C30/Br23. Dunnett’s test revealed a significant difference in these scores between baseline and 3 months after the intervention but no difference between baseline and 6 months after the intervention.ConclusionThese results suggested the possibility of a short-term effectiveness of the intervention; however the results were inconclusive because of selected small samples.

A randomized, double-blind, placebo-controlled phase III trial of zoledronic acid in the prevention of skeletal complications in Japanese women with bone metastases from breast cancer

668 Background: In Western populations, zoledronic acid (ZOL) has been proven effective for the prevention of skeletal related events (SREs) from bone metastases. For breast cancer patients, ZOL was shown to be superior to pamidronate. However, the efficacy of ZOL is unknown in Japanese patients. We report here data from the first randomized, placebo-controlled study of ZOL in Japanese patients. METHODS Japanese women with bone metastases from breast cancer were randomized to either ZOL 4mg i.v. infusion over 15 min every 4 weeks or placebo (P). The primary efficacy endpoint was SRE rate ratio (ratio of number of SREs per year for ZOL-treated patients over that for placebo) at 1 year. SREs included pathologic fractures, radiation to bone, spinal cord compression, and surgery to treat or prevent fractures. Secondary endpoints included proportion of patients with ≥1 SRE, time to first SRE and multiple event analysis (MEA: A-G model). Tumor induced hypercalcemia was included in the SRE composite in secondary endpoints. Safety was assessed according to NCI-CTC. RESULTS 227 patients (median age 53 years) were accrued to the study with 114 in the ZOL arm and 113 in the P arm. Patients were well matched with regard to baseline clinical characteristics. The primary endpoint, SRE rate ratio was 0.61 (p=0.027), indicating that SRE rate was reduced by 39% with ZOL. Proportions of patients with ≥1 SRE were 30.7% and 52.2% for the ZOL and P group, respectively (p=0.001). Median time to first SRE were 360 days in the P group while it did not reach in the ZOL group (p=0.004). Risk ratio of ZOL to P was 0.56 by MEA (p=0.009). ZOL was well tolerated. The most common adverse effects observed more frequently in the ZOL vs. P group were pyrexia (55% vs. 33%), fatigue (44.5% vs. 31.9%) and arthralgia (21.1% vs. 15.9%). One patient in the ZOL group (0.9%) experienced increased serum creatinine. CONCLUSIONS ZOL 4mg demonstrated significant clinical efficacy in Japanese patients for preventing skeletal complications with bone metastases, with an overall 44% reduction in the risk of experiencing SREs as shown by MEA. [Table: see text].

Salvage Esophagectomy for Recurrent Tumor after Radical Chemo-Radiotherapy

近年, 局所進行例のほか, 切除可能な食道癌に対しても根治的な化学放射線療法 (chemoradiotherapy;CRT) が選択され, その結果salvage手術を経験する機会が多くなっている.当施設ではこれまでに根治的CRT後の食道癌に対するsalvage手術を5例経験した.全例臨床病期III期以上の進行症例で, 初回治療としてFP療法と放射線治療の同時併用療法を施行し, CR 1例, PR 4例であった.Salvage手術は, 3例は局所の再発・再燃に対して行い, 2例はCRT後の残存病巣の切除目的にて行った.手術は全例, 右開胸開腹食道亜全摘・3領域郭清と大彎側胃管による後縦隔経路再建を施行した.5例中2例に術後合併症を認めたが, 縫合不全はなく, また手術関連死もなかった.現在4例が無再発生存中である.当施設においてはsalvage手術により良好な成績が得られているが, 今後その意義を明らかにするために, 症例の蓄積と検討が必要である.

Report of Five Cases of Acute Pulmonary Embolism after Gastrointestinal Surgery

The incidence of pulmonary embolism(PE)has been increasing although it considered lower in Japan than in the West. We report 5 cases of PE after gastrointestinal surgery from January 1994 to March 2001 representing 0.2% of surgically treated patients during that period. In 4 cases except a light PE patient it oc‑ curred when they first walked after surgery. 1 case of PE occurred despite using intermittent pneumatic compression(IPC)during surgery to prevent it. We diagnosed PE by pulmonary perfusion scintigraphy or thoracic computed tomography(CT) . We conducted anticoagulant therapy using heparin and thrombolytic therapy using urokinase or tissue plasminogen activator(t‑PA)immediately after the diagnosis. We could save 3 patients including 1 with light PE and 2 treated by t‑PA. Serious complications in thrombolytic therapy occurred in 3(2 massive bleedings and 1 extensive cerebral hemorrhage). PE is the most critical complication after gastrointestinal surgery so more prevention as low‑dose unfractionated heparin or elastic stockings may be necessary in high risk group of PE.