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.     

Experimental studies concerning comparison of the effect on the intestine between antitumor agents and radiation

Though radiotherapy combined with chemotherapy is used increasingly more frequently in the recent treatment of malignant tumors, very little is known about what dose of an antitumor agent equals what radiation dose in effect. We tried to determine those radiation doses which are required to produce the same effect as certain specific doses of antitumor agents (isoeffective dose) by studying the early effects of radiation and drugs chiefly on the intestine of dd strain mice. Parameters used were food consumption, body weight change, 3H-TdR radioactivity in the intestine and the labelling index of intestinal crypt cells. The results were as follows: 1) To determine that radiation dose which is equal to a drug dose (1/2 its LD50) in systemic effect, body weight change and food consumption were suggested to be useful parameters. 2) To determine that radiation dose which is equal to a drug dose in the effect on a specific organ, parameters suitable for the target cells must be selected. For evaluating the effect on the intestine, the labelling index of intestinal epithelium was a useful parameter. 3) The results of treatment with combined radiation and slight amounts of drugs suggested that the degree of aggravation of radiation injury due to drugs might vary with the time of drug administration. 4) Graphic representation of the severity of injury as indicated by parameters enabled us to grasp visually the characteristics of drugs.     

Preservation of tubal function following methotrexate treatment for ectopic pregnancy

To evaluate methotrexate (MTX) administration as a conservative treatment for ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of MTX treatment for tubal pregnancies at our department between December 1985 and December 2003, and compared its pregnancy prognosis with that of laparoscopic salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 % and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively, after the salpigotomy. These results suggest that MTX treatment is comparable to the more conservative operation. To clarify the (dys/) function of the ectopic implantation tubes and MTX-treated tube (s), we excluded patients who had a contra-lateral healthy tube, and extracted 40 patients as "the affected tube group", where the pregnancy-related parameters were not adversely affected. The findings suggest that MTX is not necessary to preserve tubal function.     

Role of Predictive Value of the Modified Glasgow Prognostic Score for Later-line Chemotherapy in Patients With Metastatic Colorectal Cancer

Background

Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated.

Clinical usefulness of chemosensitivity testing using the MTT assay

The results of in vitro chemosensitivity testing using the MTT assay of tumor cells from 140 patients were analyzed with reference to the clinical antitumor effects of the chemotherapy. One hundred and twenty-four (88.6%) of 140 specimens were successfully tested by the method of Mosmann (J Immunol Methods 65:55-63, 1983) with some modifications. When the results of the assay were compared with the clinical effects of chemotherapy in 22 patients with remaining measurable tumor lesions, the overall prediction rate was 86.4% (19/22). Among 31 patients with stage III-V gastric and colorectal carcinomas without remaining measurable tumor lesions, the survival rate of nine patients treated with drugs shown to be effective in the assay was significantly (P less than 0.05) better than that of 22 patients treated with drugs shown to be ineffective.     

Antitumor activity and pharmacokinetics of a morpholino-anthracycline derivative (KRN8602) against human breast carcinoma xenografts serially transplanted into nude mice

The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.     

Pulmonary embolism and cerebral venous thrombosis after thoracoscopic surgery for benign pulmonary disease

A-76-year-old woman consulted for open biopsy for a pulmonary mass. Thoracoscopic wedge resection was performed. The lesion was histologically diagnosed as nonspecific inflammation. On the first postoperative day (POD1), the patient lost consciousness transiently. Eleven hours after the first stroke, the patient experienced a second stroke together with hypoxia. Pulmonary perfusion scan on POD2 showed multiple perfusion defects, and the patient was diagnosed with pulmonary embolism (PE). Thrombolitic therapy was started. Neurological symptoms didn’t improve, and cerebral angiography on POD3 showed delayed perfusion in superficial veins. The patient was diagnosed with cerebral venous thrombosis (CVT). Thrombolytic and anticoagulant therapy had been continued, and the patient was found to have hemorrhagic cerebral infarction on POD11. After persistent therapy, the patient was discharged on POD120. Although both PE and CVT are rare complications after thoracic surgery, we must consider these complications in patients undergoing thoracic operations including thoracoscopic surgery.