Hypertension and Proteinuria as Predictive Factors of Effects of Bevacizumab on Advanced Breast Cancer in Japan.

Bevacizumab (BV), an inhibitor of vascular endothelial growth factor, is used in combination with paclitaxel (PTX) to treat advanced breast cancer. Hypertension and proteinuria are characteristic adverse events of BV therapy. We assessed the potential of these adverse events as predictors of BV treatment responses. Our results revealed that groups that developed hypertension and proteinuria early (by day 56) had a stronger antitumor response (Fisher's exact test p<0.05). However, no significant difference was observed in progression-free survival (the Kaplan-Meier method and Log-rank test). As a reference, age, the treatment line, subtypes, liver and renal function, diabetes mellitus and hyperlipidemia history, body mass index, influencing concomitant medicine, average relative dose intensity and hematotoxicity did not significantly differ between groups with or without hypertension and with or without proteinuria. These results indicate the potential of the development of hypertension and proteinuria as predictors of improved outcomes with PTX plus BV therapy in patients with breast cancer. However, since both adverse events may preclude the continuation of treatment, their earlier management may be required.

Detection of colorectal cancer using ¹8F-FLT PET: comparison with ¹8F-FDG PET.

OBJECTIVE: We investigated the feasibility of 3'-deoxy-3'-¹8F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of colorectal cancer, in comparison with 2-deoxy-2-¹8F-fluoro-D-glucose (FDG) PET, and investigated correlation of the two radiotracers used with proliferative activity as indicated by Ki-67 index. METHODS: A total of 26 patients with newly diagnosed colorectal cancer were examined with FLT PET and FDG PET. Tumor lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. RESULTS: In all 26 patients, colorectal cancers were detected by both FLT PET and FDG PET. The mean (± SD) values of FLT SUV in colon cancer (5.4 ± 2.4) and in rectal cancer (5.6 ± 1.3) were significantly lower than the corresponding values of FDG SUV (12.4 ± 6.3 and 12.5 ± 4.7, respectively) (P < 0.003). There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. CONCLUSION: Although uptake of FLT was found to be significantly lower than that of FDG, both FLT PET and FDG PET were able to detect colorectal cancers in all 26 patients. Neither of the two radiotracers used was correlated with proliferative activity.

3'-Deoxy-3'-18F-fluorothymidine as a proliferation imaging tracer for diagnosis of lung tumors: comparison with 2-deoxy-2-18f-fluoro-D-glucose.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of 3'-deoxy-3'-F-fluorothymidine (FLT) positron emission tomography (PET) for detection of lung tumor in comparison with 2-deoxy-2-F-fluoro-D-glucose (FDG) PET. METHODS: Fifty-four patients with newly diagnosed pulmonary nodules on chest computed tomographic (CT) scan suggestive of a malignant tumor were examined with both FLT and FDG PET. The intensity of uptake in lung tumors was scored. For visualized lesions, the maximum standardized uptake value (SUV) was calculated. RESULTS: Thirty-six patients were found to have lung cancer; and 18, benign lesions. Using visual analysis, the sensitivity of FLT PET for detection of lung cancer was 83%; the specificity, 83%; and the accuracy, 83%. The corresponding values for FDG PET were 97%, 50%, and 81%, respectively. The specificity of FLT PET was significantly higher than that of FDG PET. The uptake of FLT in lung cancer was significantly lower than that of FDG. Using semiquantitative analysis, the sensitivity of FLT was 86%; the specificity, 72%; and the accuracy, 81%. The corresponding values for FDG were 89%, 67%, and 81%, respectively. CONCLUSIONS: These preliminary results indicate that FLT PET may be specific for malignant tumors although uptake of FLT in lung cancer was significantly lower than that of FDG.

Comparison of (18)F-FLT PET and (18)F-FDG PET for preoperative staging in non-small cell lung cancer.

PURPOSE: The nucleoside analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) has been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively compared the diagnostic efficacy of FLT PET with that of 2-deoxy-2-(18)F-fluoro-D-glucose (FDG) PET for the preoperative nodal and distant metastatic staging of non-small cell lung cancer (NSCLC). METHODS: A total of 34 patients with NSCLC underwent FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. The PET images were evaluated qualitatively for regions of focally increased metabolism. For visualized primary tumors, the maximum standardized uptake value (SUV) was calculated. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings reference standards. RESULTS: For the depiction of primary tumor, sensitivity of FLT PET was 67%, compared with 94% for FDG PET (P = 0.005). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for lymph node staging on a per-patient basis were 57, 93, 67, 89, and 85%, respectively, with FLT PET and 57, 78, 36, 91, and 74%, respectively, with FDG PET (P > 0.1 for all comparisons). Two of the three distant metastases were detected with FLT and FDG PET. CONCLUSION: In NSCLC, FLT PET showed better (although not statistically significant) specificity, positive predictive value and accuracy for N staging on a per-patient basis than FDG PET. However, FDG PET was found to have higher sensitivity for depiction of primary tumor than FLT PET.

[Optimum preparation of levocarnitine chloride solution in the hospital pharmacy].

Levocarnitine chloride is used for the therapeutic purpose of levocarnitine deficiency. For infants, however, levocarnitine chloride tablets must be crushed to avoid difficulties associated with swallowing, and also to administer an appropriately low dosage. Since the tablet is extremely hygroscopic and sour, it is dissolved in water containing simple syrup after crushing. In this study we investigated the stability of the drug after dissolution to optimize its preparation for clinical use. It was shown to be stable for at least 90 days after preparation, and microbes did not grow in 1-10% (w/v) solutions (pH 2.0-2.5) regardless of the presence or absence of simple syrup. Furthermore, the autoclaved levocarnitine chloride solution was as stable as the non-autoclaved one. In conclusion, the method employed in our hospital for the preparation of levocarnitine chloride for infants is appropriate and is recommended as a standard medicine supply method among different facilities.

[Status of achievement of the aseptic preparation method for total parenteral nutrition expected by physicians and nurses].

In most medical institutions, although total parenteral nutrition (TPN) should be prepared by pharmacists in sterile condition, nurses actually perform this procedure in hospital wards. The currently growing belief is that pharmacists should prepare all preparations for injection using aseptic technique. Therefore, we conducted a survey on how physicians and nurses feel about methods of preparation of TPN and other agents for injection. The results demonstrated that physicians and nurses desired pharmacists to prepare all agents for injection according to prescriptions using aseptic technique, under pharmacological control and on a 24-hours basis. Based on these results, we examined a method to realize this expectation to the extent possible in our hospital and applied it when aseptic TPN preparations were extended to include relatively stable patients requiring TPN in all hospital wards. The number of TPN preparations increased steadily. The mean number of aseptic TPN preparations after stabilization of this method was 1214 a month. A total of 48% of all TPN solutions required were prepared in aseptic condition, with an average of 4.4 vials of agents mixed per prescription. For TPN base solution, 71% of a double--bag preparation consisting of electrolytes, saccharides, and amino acids was used. It was prepared in the wards most often for the reason, "described as an unscheduled prescription". The cost of consumables required for aseptic preparations was approximately 1.7 times the insurance coverage for addition of aseptic preparations. The physicians and nurses supported the method used by the pharmacists. To ensure complete aseptic preparation of injections by pharmacists, additional pharmacists, a review on their working system, more insurance points, and a broader range of insurance coverage may be required.