A prospective observational study to evaluate G-CSF usage in patients with solid tumors receiving myelosuppressive chemotherapy in Italian clinical oncology practice.

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

BACKGROUND: We investigated pretreatment fasting glucose as a predictor of patients' important outcomes in breast and colorectal cancers undergoing targeted therapies. PATIENTS AND METHODS: In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan-Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified by primary site of cancer and including gender, age and body mass index. RESULTS: The median follow-up was 20 months (1-128). At 60 months, 65% of patients in the lowest tertile of fasting glucose did not experiment disease progression compared with 34% in the highest tertile (P=0.001). Seventy-six percent of females in the lowest tertile showed no progression compared with 49% in the top tertiles (P=0.015). In multivariate analysis, fasting glucose was a significant predictor of time to disease progression only in breast cancer patients in the first tertile compared with the third (P=0.017). CONCLUSIONS: We found evidence of a predictive role of pretreatment fasting glucose in the development of resistance in breast cancer patients treated with targeted agents. Prospective studies are warranted to confirm our findings.

Safety of cisplatin after severe hypersensitivity reactions to carboplatin in patients with recurrent ovarian carcinoma.

BACKGROUND: Carboplatin is a milestone drug against ovarian carcinoma; it is used both in front-line and second-line chemotherapy. Hypersensitivity reactions to carboplatin may occur during the treatment as salvage therapy. The purpose of this study was to describe the feasibility of the replacing of carboplatin with cisplatin in patients presenting with severe hypersensitivity reactions to carboplatin. PATIENTS AND METHODS: Ten consecutive patients with platinum-sensitive, recurrent ovarian carcinoma, presenting with moderate/severe hypersensitivity reactions to carboplatin were treated with cisplatin 60 mg/m2 from January 2000 to December 2002. Hypersensitivity reactions consisted of respiratory distress (chest tightness, wheezing, dyspnea), urticaria/erythema with tachycardia, facial swelling and hypotension. RESULTS: The total number of cisplatin cycles given was 44 (range 2-5). The treatment with cisplatin was generally well tolerated. No serious allergic reactions occurred. A mild allergic reaction was recorded (urticaria) in only one case, after one cycle of cisplatin, and the patient was not rechallenged because of progressive disease. No reductions of chemotherapy doses were needed. CONCLUSION: To date, platinum-based regimens remain the most effective treatment in recurrent platinum-sensitive ovarian cancer with a high rate of objective responses. Although our experience is limited, we suggest that, under anesthesiologic surveillance and providing immunologic blockade, the replacement of carboplatin salvage therapy with cisplatin can be considered a safe therapeutic strategy in patients who cannot continue carboplatin due to allergic reactions.

Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas: five-year results with epirubicin and ifosfamide.

BACKGROUND: Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas (STS) may provide some advantages for facilitating the surgical resection of the tumor and for disease control. However its role as induction therapy before surgery should still be proved. PATIENTS AND METHODS: Twenty-one patients with intermediate/high-grade STS and tumor size > or = 5 cm were consecutively treated from 1997 to 2001 with neoadjuvant chemotherapy based on epirubicin 60 mg/m2/day on days 1 and 2 and ifosfamide 1.8 gr/m2/day on days 1 through 5 every three weeks. Evaluation of objective tumor response and toxicity were carried out according to WHO criteria. RESULTS: Nine partial responses were documented; stable disease in 11 patients, progressive disease in one patient. Apart from nine cases of grade 4 neutropenia, the treatment was generally well-tolerated. Twelve patients underwent conservative and limb salvage surgery. CONCLUSION: This therapeutic approach seems to be effective in facilitating surgery. Neutropenia was the most significant toxicity but it was preventable or medically treatable with G-CSF support.

High-dose folinic acid (FA) and fluorouracil (FU) plus or minus thymostimulin (TS) for treatment of metastatic colorectal cancer: results of a randomized multicenter clinical trial.

The purpose of this study was to ascertain the possible protective effect of thymostimulin (TS) on chemotherapy-induced leukopenia and related febrile episodes, beside the potential of improving therapeutic efficacy and tolerability of high-dose folinic acid (FA) plus fluorouracil (FU) in metastatic colorectal cancer. In 211 evaluable patients the objective responses were 19/105 (18%) in the FA-FU arm versus 32/106 (30%) obtained with the same regimen plus TS. The difference was statistically significant (p = 0.02). No difference was observed in terms of hematological toxicity, while the TS treated patients experienced a significantly lower incidence of mucositis and diarrhoea (p = 0.03). No significant differences were recorded in the incidence of febrile episodes and other treatment-related toxicities. The possibility of improving response to chemotherapy in advanced colorectal cancer without increasing systemic toxicity is particularly interesting and deserves further attention.

Neuroendocrine (Merkel-cell) carcinoma of the skin. Fine needle aspiration cytology and clinicopathologic study of a case.

Neuroendocrine (Merkel-cell) carcinoma of the skin, a neoplasm usually found in elderly individuals, is often locally aggressive and has the potential to metastasize to lymph nodes and cause death. Microscopically the neoplasm is a small-cell carcinoma that involves primarily the dermis. We report a case of such a neoplasm in a 61-year-old female, stressing the possible contribution of fine needle aspiration cytology in the recognition of this neoplasm and its differentiation from other small-cell neoplasms that may involve the skin.