[A pilot study of the reduced effects of adverse events caused by oral morphine and oxycodone after rotating to fentanyl patch in patients with metastatic breast cancer].

BACKGROUND: It has been confirmed by several clinical trials that the fentanyl patch causes less adverse events than sustained-release oral morphine, and after rotation. However, there has been no evidence comparing the fentanyl patch with controlled-release oral oxycodone in terms of adverse events. PURPOSE: We prospectively investigated the reduced effects of adverse events caused by sustained-release oral morphine and controlled-release oxycodone after rotating to the fentanyl patch in patients with metastatic breast cancer. METHOD: Metastatic breast cancer patients requiring sustained-release oral morphine or controlled-release oral oxycodone(n=9, 2 taking oral morphine, 7 taking oral oxycodone, mean age, 57. 5 years)were recruited. Those experiencing adverse events from oral morphine or oral oxycodone were administered a fentanyl patch. RESULTS: The pain score was reduced significantly at the 4th week. The fentanyl patch was associated with significantly less nausea, vomiting, constipation, sleepiness and dizziness over the study period. CONCLUSION: This study suggested that the fentanyl patch can reduce adverse events caused by sustained-release oral morphine as well as controlled-release oral oxycodone.

[A case of HER2 overexpressing advanced breast cancer with CTF therapy [cyclophosphamide, pirarubicin (THPADM), fluorouracil] showed long-term effectiveness after paclitaxel shock].

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.

Preoperative dynamic lymphoscintigraphy predicts sentinel lymph node metastasis in patients with early breast cancer.

BACKGROUND: Preoperative lymphoscintigraphy is commonly used in sentinel lymph node biopsy (SLNB) for patients with early breast cancer; however, its significance to predict SLN metastasis remains to be determined. PATIENTS AND METHODS: Sixty patients were enrolled in a feasibility study of SLNB. Patients with clinically node-negative breast cancer were eligible for this study. Dynamic lymphoscintigraphy was performed before SLNB. All patients underwent SLNB followed by axillary lymph node dissection. RESULTS: A dual mapping procedure using isotope and dye injections was performed. SLNs were identified in 59 of 60 patients (98.3%), with a node-positive rate of 41.7% and a false-negative rate of 1.7%. No SLN was identified in 4 of 60 patients (6.7%) on preoperative lymphoscintigraphy. Interestingly, abnormal accumulation of the radiotracer close to hot spots was observed in 29 of 56 patients (51.8%). Lymph node metastases were detected in 18 of 29 patients (62.0%) with this pattern and 5 of 27 patients (18.5%) without this pattern (P < 0.05). Micrometastases were more frequently detected in node-positive patients without this pattern than in those with this pattern (80 vs. 16.7%). Diagnostic parameters of this pattern to predict SLN metastases, including micrometastases, were 62.1% for sensitivity, 81.5% for specificity, and 71.4% for accuracy. CONCLUSIONS: Abnormal accumulation of the radiotracer close to radioactive spots may indicate SLN metastasis. When dynamic lymphoscintigraphy shows this pattern, surgeons should consider the presence of SLN metastasis and carefully remove additional lymph nodes surrounding radioactive lymph nodes so as not to leave metastatic SLNs behind.

[Evaluation of irinotecan hydrochloride (CPT-11) and trastuzumab combination therapy as salvage treatment in patients with HER2 overexpressing metastatic breast cancer].

BACKGROUND: Though irinotecan hydrochloride(CPT-11)was approved in Japan in 1994, there have been few reports since that evaluated the efficacy of CPT-11. The position of this agent in the treatment of patients with metastatic breast cancer(MBC)is not definite. In addition, no report has been published to date about CPT-11 and trastuzumab combination therapy. PURPOSE: To evaluate retrospectively the efficacy of CPT-11 and trastuzumab combination therapy as salvage treatment in patients with human epidermal growth factor receptor 2 (HER2)overexpressing MBC. PATIENTS AND METHOD: We examined ten cases who received this therapy against MBC since February 2002 till March 2007 in our hospital. Overall response rate, change of tumor markers, time to treatment failure (TTF), time to progression( TTP), overall survival (OS)after start of CPT-11 and adverse events were examined for efficacy and tolerability. RESULTS: Median age was 57 (40-67)and median number of prior chemotherapies was 5(2-9). Though the overall response rate was 20%, some tumor reduction was observed totally in seven cases. CEA and CA15-3 were decreased in 78%(7/9)and 63%(5/8) of cases, respectively. Median TTF, TTP and OS were 3, 4, and 6 months, respectively. Adverse events included three cases of severe neutropenia, one of whom died of treatment-related sepsis. Slight diarrhea occurred in seven and severe nausea occurred in two cases. Dose modification of CPT-11 was necessary in 5 cases, and three discontinued CPT-11 administration, mainly due to easy fatigability, nausea and neutropenia. During the therapy, four cases were all inpatients, and 6 eventually became outpatients. DISCUSSION: This therapy for patients with HER2 overexpressing metastatic cancer resistant to multi-agents demonstrated a good result in terms of antitumor effect. But high tolerability could not be documented by our experience with this therapy. It was supposed that the risk management with prediction of adverse events and preparation of better supportive therapy could make for the higher tolerability of this therapy for more effective clinical use.

[A case of paclitaxel and trastuzumab-resistant recurrent breast cancer with liver metastasis responding to S-1].

We experienced a case of paclitaxel- and trastuzumab-resistant recurrent breast cancer with liver metastases showing significant improvement by S-1. A 76-year-old woman was diagnosed with left breast cancer (T2N1M0, Stage II B). She received total mastectomy and CEF (cyclophosphamide 500 mg/m(2), epirubicin 60 mg/m(2), 5-FU 750 mg/m(2)) as adjuvant chemotherapy in March 2004. But twelve months later, she was referred to our clinic for management of lung and left supraclavicular lymph node metastases. Then weekly paclitaxel (80 mg/m(2)) and trastuzumab were started. After 2 cycles of weekly paclitaxel and trastuzumab treatment, lung and lymph node metastases were reduced and the patient showed a clinical response (CR), so she was treated by trastuzumab only. But seven months later, she was diagnosed as a recurrence of liver metastases. She was treated by combined paclitaxel and trastuzumab again, but liver metastases and tumor marker were progressive. S-1 was administered orally 100 mg/day every day for 4 weeks, followed by a 2-week rest interval as 1 cycle, and trastuzumab was injected at 2 mg/kg/week for every weeks. After 2 courses of the treatment, the level of tumor marker and tumor size of liver metastases were reduced. Only rash (grade 1) was observed during treatment. The treatment of S-1 is thought to be effective for taxane-resistant recurrent breast cancer.

[Efficacy of sequential treatment with anastrozole following exemestane compared with exemestane following anastrozole in patients with metastatic breast cancer].

BACKGROUND: There are three third-generation aromatase inhibitors (AI) available in Japan. Though it is supposed that they can be administered sequentially because of their little cross-resistant effect, it is not definite which sequential treatment is best. PURPOSE: To examine retrospectively the difference in efficacy by the AI sequence when anastrozole ( ANA) and exemestane (EXE) are clinically administered sequentially for patients with metastatic breast cancer. PATIENTS: We examined 22 patients with metastatic breast cancer administered ANA alone as first-line AI treatment, EXE alone as second-line (A--> E group), and 13 patients given EXE alone as first-line AI treatment (E --> A group) since December 2002 in our hospital. METHOD: In the A --> E and E --> A group, we examined overall response rate, clinical benefit (CB) rate, time to progression (TTP) for the first- and second-line treatment, respectively, overall survival (OS) after starting AI and successive efficacy of the two AIs. RESULTS: There were no significant differences between the two groups in patient characteristics and history of prior treatments. Overall response rate of the first-line treatment in the A--> E and the E--> A group was 31.8% and 38.5%, and the CB rate was 68.2% and 53.8%, respectively. Overall response rate of the second-line treatment in the A --> E (22 cases) and the E --> A (3 cases) group was 13.6% and 0%, and the CB rate was 36.4% and 33.3%, respectively, reflecting no particular differences. In the A --> E group, five (33.3%) among 15 cases obtained CB by EXE and three (42.6%) among 7 cases who did not obtain CB by ANA did so by EXE. Also, in the E--> A group, one among 3 cases who did not obtain CB by EXE did so by ANA. No significant differences were observed in TTP and OS between the two groups. CONCLUSION: When ANA and EXE are administered sequentially, no particular difference in efficacy occurs due to the sequence. In some cases, 2 agents become effective successively, and cases resistant to first-line treatment can expect efficacy from second-line treatment. Sequential treatment with the two agents seems to provide very significant efficacy in clinical practice regardless of the order of administration.

[Docetaxel administration for radioiodine-resistant patients with metastatic papillary thyroid carcinoma].

We report three radioiodine-resistant patients with metastatic papillary thyroid carcinoma administered docetaxel. Patient 1: Bi-weekly docetaxel was administered to a 67-year-old woman with clavicle, cervical lymph node and lung metastases that had progressed after external irradiation and radioiodine therapy. Stable disease was maintained for 18 months without elevation of serum thyroglobulin. Patient 2: Bi-weekly docetaxel was administered to a 72-year-old man with lung metastases that had progressed after radioiodine therapy. Stable disease was maintained for 14 months. Patient 3: Bi-weekly docetaxel was administered to a 58-year-old woman with lung metastases that had progressed after radioiodine therapy. Stable disease was maintained for 18 months with slight reduction of serum thyroglobulin. In all three patients, doubling time of tumor growth was revealed to be far prolonged after docetaxel administration without distinct adverse events. Since no effective systemic treatment has been established for radioiodine-resistant patients with metastatic papillary thyroid carcinoma,docetaxel therapy was supposed to be a viable alternative for them.

[Therapeutic efficacy of capecitabine on advanced and recurrent breast cancer with special reference to time to progression].

We investigated 29 patients with advanced and recurrent breast cancers who underwent capecitabine therapy in the department. Patients'backgrounds: 41-89 years of age (median, 57 years of age). Advanced breast cancers, 5; recurrent breast cancers, 24. PS< or =2 in 18 cases and PS 3< or =in 11 cases. Eighty-six percent of patients were positive for ER and/or PgR. Multiorgan metastases occurred in 22 cases; bone metastases, 22 cases; lymph node metastases, 12 cases; skin metastases, 11 cases; lung metastases, 10 cases. The rate of patients who received chemotherapy was 93%, and the rate of those who received endocrinotherapy was 90%. Therapeutic response rate was CR in 1 case, PR in 5 cases, long SD in 5 cases, SD in 10 cases and PD in 8 cases, indicating a response rate of 20.7% and a clinical benefit rate of 37.9%. Time to progression (TTP) was 1-15 months (the median time, 4 months). Overall survival time (OS) was 2-23 months (median length, 12 months). OS was significantly longer in patients who had therapeutic effects than in patients with no such effects. TTP was significantly longer in patients who had therapeutic effects and in those who had longer SD than in patients with no such effects. OS was significantly longer in patients who had TTP of 6 months or longer. Clinical benefit (presence vs. absence) and PS (< or =2 vs. 3< or =) were independent factors affecting TTP. Capecitabine is expected to prolong the length of survival in patients who are able to continue treatment for 6 months or longer.

Combined measurement of serum sialyl Lewis X with serum CA15-3 in breast cancer patients.

BACKGROUND: Serum CA15-3 has been one of the most reliable tumor markers used in monitoring breast cancer patients; however, its sensitivity in detecting metastases is limited. To increase its sensitivity, the combined measurement of other tumor markers with CA15-3 was investigated. METHODS: Serum CA15-3, carcinoembryonic antigen (CEA) and sialyl Lewis X (CSLEX) were simultaneously measured in a prospective series of 455 postoperative breast cancer patients with or without metastasis. The diagnostic parameters sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for detecting metastases were compared. The correlation of values between pairs of tumor markers was analyzed. The efficacy of combined measurement of two different tumor markers was also evaluated. RESULTS: The sensitivity for detecting metastases was 61.5, 56.9 and 52.3%; specificity was 97.2, 93.6 and 96.2%; PPV was 78.4, 59.7 and 69.4%; NPV was 93.8, 92.9 and 92.4%; and accuracy was 92.1, 88.8 and 89.9% for CA15-3, CEA and CSLEX, respectively. The values for CA15-3 were significantly correlated with those for CEA (P < 0.001) but not those for CSLEX. The combined measurement of CSLEX and CA15-3 increased the sensitivity by 17.0% but that of CEA and CA15-3 increased the sensitivity by only 10.8%. All diagnostic parameters for the combined measurement of CSLEX and CA15-3 were higher than those for the combined measurement of CEA and CA15-3. CONCLUSIONS: These findings suggest that CSLEX may be more useful than CEA in combination with CA15-3 in monitoring breast cancer patients. The results of this study suggest that CSLEX may be more useful than CEA in combination with CA15-3 in monitoring breast cancer patients.

[Undifferentiated carcinoma(endocrine cell carcinoma) of the colon].

Recently, several cases of undifferentiated carcinoma and endocrine cell carcinoma are reported in the Japanese literature. In some reports, it is seemed to be confused in differentiating the diagnosis of these carcinomas, and considered that these carcinomas are in the same entity. When undifferentiated carcinoma of the large intestine is indicated, aggressive exploration such as immunohistochemical staining entertaining a possible existence of endocrine cell carcinoma is essential. Both undifferentiated carcinoma and endocrine cell carcinoma have the least favorable prognosis and effective multimodal therapy, including operation and chemoradiotherapy should be established.