[Neuropathic pain in oncology. Novel evidence for clinical practice]. / Il dolore neuropatico in oncologia. Nuove evidenze per la pratica clinica.

Neuropathic pain is usually considered an "hard pain" both for the intrinsic difficulties in a correct diagnosis, and for the modest efficacy of the most part of conventional treatments. The most frequently used drugs in clinical practice are tricyclic antidepressants and anticonvulsants, while a minor role is reserved to NSAIDs or to strong opiates. Aim of our work was to systematically analyze all the evidences of literature about the treatment options against neuropathic pain in oncology, focusing our attention upon the efficacy and the safety of the different therapeutic options assessed as Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH). A critical analysis of literature was finally performed using the GRADE system. On the basis of our review and the NNT and NNH ratio, gabapentin, pregabalin and strong opiates seem to be the most effective and well tolerated options against neuropathic pain in oncology, while carbamazepine, amitryptiline, tramadol and NSAIDs do not seem to be valid options in front line approach against oncologic neuropathic pain, either for a minor efficacy or for an unfavorable safety profile. Further trials comparing the different effective options are needed to better define the correct approach against neuropathic pain in oncology.

Toxic encephalopathy in elderly patients during treatment with capecitabine: literature review and a case report.

Capecitabine is now-a-days rapidly replacing 5-Fluorouracil in daily clinical practice. Neurologic toxicity during a treatment with fluoropyrimidines, as 5-fluorouracil, represents a well-known side-effect, largely described in literature. Central nervous system (CNS) toxicity, mainly encephalopathy with or without seizures, occurs occasionally even when conventional doses are used. CNS toxicity incidence increases markedly when the blood-brain barrier is either overwhelmed or bypassed (Hildebrand J. Neurological complications of cancer chemotherapy. Curr Opin Oncol 2006; 18: 321-324). Peripheral nervous system (PNS) toxicity is more common because proximal and distal extremities of the peripheral nerves are not protected by a blood-brain like barrier and peripheral neuropathy remains a major limiting factor for the administration of conventional doses of several agents (Saif W, Wood TE, McGee PJ and Diasio RB. Peripheral neuropathy associated with capecitabine, Anticancer Drugs 2004;15: 767-771). Capecitabine is a prodrug of 5-fluorouracil, more easily administered by mouth; its transformation in 5-fluorouracil is performed in the liver. There are only a few reports on the toxic neurological side-effects of capecitabine. We describe in our report a rare case of toxic encephalopathy in a 82-year-old female, with a brief review of literature. In the literature reviewed, we found 12 neurologic episodes due to capecitabine lasting between a few days till some months. All clinical symptoms of the cases described in literature, obtained a complete regression with the discontinuation of capecitabine. A relation was not found with dihydropyrimidine dehydrogenase (DPD) mutation, also if pharmacologic and pharmacogenetic assessment should be done for this drug, especially in old patients. Toxic encephalopathy represents a rare event during capecitabine treatment and on the bases of the data found, is fairly managed in the clinical setting. The knowledge of the natural history of the toxic effect allows the use of the drug also in old patients.

Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report.

INTRODUCTION: Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. CASE PRESENTATION: We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. CONCLUSIONS: It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.

Zoledronic acid treatment at home: safety data from an observational prospective trial.

BACKGROUND: To prospectively assess feasibility, side effects, and safety of a home treatment with zoledronic acid in patients with bone metastases confined to home. PATIENTS AND METHODS: Forty-two patients with bone metastases (15 males and 27 females; mean age, 72 years; range, 48-86), confined to home because of functional impairment or low performance status, were enrolled into the trial. They were included in a comprehensive program of home care, and were treated with zoledronic acid, 4 mg. Primary end point of this observational trial was the safety assessment of the treatment at home; secondary end points were the clinical assessment of the time to treatment discontinuation and the definition of a pattern of patients who could benefit by a home treatment with intravenous bisphosphonates. RESULTS: Nineteen patients had breast cancer; 7, multiple myeloma; 5, non-small-cell lung cancer; 4, renal cancer; 4, prostate cancer; 1, thyroid cancer; 1 non-Hodgkin's lymphoma; and 1 soft tissue sarcoma. On the whole, 220 home treatments were administered in 3 years, with a median of 4 administrations per patient (range, 1-28). Median time to treatment discontinuation was 130 days. The treatment was interrupted for worsening of the performance status in 30 patients (71.4%), length of the treatment greater than 24 months in 2 patients (4.8%), hypocalcemia in 1 patient (2.4%), renal failure in 1 patient (2.4%). No difference in median time to treatment discontinuation was observed among patients with breast cancer, multiple myeloma, or other tumors in univariate analysis. Multivariate analysis showed no prognostic significance for kind of tumor, age at the time of entering the trial, gender, and number of extraosseous sites of disease. No acute major side effects were observed during the treatment, and the treatment had to be interrupted for side effects in 2 patients (4.8%). One patient had jaw osteonecrosis some months after the treatment was stopped. CONCLUSIONS: The home treatment with zoledronic acid seems safe. The appropriate use of biphosphonates in such a new setting needs a criterion to identify the subset of patients with bone metastases confined to home who can really benefit by this treatment.