Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed.

We present a case of interstitial nephritis and nephrogenic diabetes insipidus (NDI) in a patient treated with pemetrexed (500 mg/m(2)) for non-small cell lung cancer. Renal impairment and diabetes insipidus appeared after the first treatment cycle while he totally received four cycles of chemotherapy. There was not any significant myelosuppression and the patient was on regular supplementation with folic acid and vitamin B(12). He was not on any other medications and he did not receive any nephrotoxic agents. Kidney biopsy showed acute tubular necrosis together with interstitial inflammatory infiltrate of mononuclear cells and interstitial fibrosis occupying 25% of the cortex. There was not any improvement of renal function after a 2-week trial of oral prednisone. In the present case report, we review the literature for pemetrexed-induced renal toxicity and the possible mechanisms involved.

Quantification of tumor microvascularity with respiratory gated contrast enhanced ultrasound for monitoring therapy.

The aim of this feasibility study was to evaluate the response to cytotoxic and antiangiogenic treatment of colorectal liver metastasis using respiratory gated contrast enhanced ultrasonography. Seven patients were monitored with contrast enhanced ultrasound. Sulfur hexafluoride filled microbubbles (SonoVue; Bracco S.P.A., Milan, Italy) were used as contrast agent and the scans were performed with a nonlinear imaging technique (power modulation) at low transmit power (MI=0.06). The mean image intensity in the metastatic lesion and in the normal liver parenchyma were measured as a function of time and time-intensity curves from linearized image data were formed. A novel respiratory gating technique was utilized to minimize the effects of respiratory motion on the images. A reference position of the diaphragm (or other echogenic interface) was selected and all frames where the diaphragm deviated from that position were rejected. The wash-in time (start of enhancement to peak) of metastasis and adjacent normal liver parenchyma was measured from time-intensity curves. The ratio of wash-in time of the lesion to that of the normal parenchyma (WITR) was used to compare the perfusion rate. In a reproducibility study (five patients), the average deviation of WITR was found to be 9%. There was an increase in the WITR for patients responding to treatment (mean WITR increase of 17% after first dose of treatment and 75% at the end of the therapy). In four out of five patients (80%) responding to therapy WITR predicted their response from the first treatment. All six patients that responded to therapy by the end of the therapy cycle (6-9 doses) were correctly predicted by using WITR. The WITR may be a new surrogate marker indicative of early tumor response for colorectal cancer patients undergoing cytotoxic and antiangiogenic therapy. (E-mail: maverk@ucy.ac.cy).

Docetaxel and gemcitabine combination, as first-line treatment, in patients with extensive disease small-cell lung cancer. A phase II study of the Hellenic Cooperative Oncology Group.

There is some evidence that taxanes and gemcitabine are effective antitumor agents against small-cell lung cancer (SCLC). A total of 20 chemotherapy-naive patients with extensive disease (ED) SCLC, were treated as a part of the first step of a phase II study, with docetaxel 50 mg/m(2) and gemcitabine 1000 mg/m(2), both administered on day 1 and 8 every 3 weeks up to a total of six cycles. For patients who progressed after the first cycle or had stable disease after the second cycle of chemotherapy, protocol treatment was stopped and further treatment with the standard cisplatin or carboplatin-etoposide combination was administered. Patients were in the vast majority male smokers with a good performance status. A total of 72 cycles was delivered while patients managed to receive the 78 and 84% of the planned dose of docetaxel and gemcitabine, respectively. Only six patients responded partially and the trial ended prematurely since at least seven responses were required among the first 19 patients. With a median follow-up of 13 months, median time to progression (TTP) was 8 months and median survival 9.6 months. Hematological and non-hematological toxicity was generally acceptable while patients tolerated their treatment reasonably well. In conclusion, docetaxel-gemcitabine showed a modest response rate in chemotherapy-naive patients with ED SCLC.