Stefano Luzi Fedeli

Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial.

PURPOSE Diarrhea is a prominent feature of fluorouracil (5FU) gastrointestinal toxicity, especially when 5FU is combined with leucovorin (LV) or interferon (IFN). No treatment for this condition has been well defined, although drugs, such as diphenoxylate or loperamide, generally are used. The efficacy of octreotide in the treatment of 5FU-induced diarrhea recently has been reported. We performed a randomized trial that compared octreotide with loperamide, the drug most commonly used for therapy for this disorder. PATIENTS AND METHODS Forty-one patients with grade 2 (four to six stools per day) or grade 3 (seven to nine stools per day; National Cancer Institute toxicity criteria) diarrhea after chemotherapy with a 5FU-containing regimen for colorectal cancer in 28 cases, gastric cancer in six cases, pancreatic cancer in five cases, and breast cancer in two cases, were entered onto the study. Twenty-one patients received octreotide at a dosage of 0.1 mg subcutaneously twice per day for 3 days, and 20 patients received loperamide 4 mg orally initially and then 2 mg every 6 hours for 3 days. The two arms were comparable for age, sex, and primary tumor. Patients were evaluated for response each treatment day; all patients were assessable. RESULTS Diarrhea resolved in 19 patients in the octreotide arm (one within the first day; four within the second day; and 14 within the third day) versus only three (all after the third day of therapy) in the loperamide arm (P < .005). Median frequency of stools in the 3 days of therapy was four, three, and zero in the octreotide arm and five, five, and five in the loperamide arm. No side effects were observed in both arms. Ten patients on the loperamide arm and only one on the octreotide arm required hospitalization for parenteral replenishment of fluids and electrolytes. CONCLUSION Octreotide seems to be more effective than loperamide in control of diarrhea and elimination of the need for replenishment of fluids and electrolytes.

Control of Chemotherapy-Induced Diarrhea with Octreotide

Cisplatin-related diarrhea is a relatively common complication in the clinical management of cancer patients and until now no treatment for this condition has been identified. Octreotide has been repo

Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5-fluorouracil

Chemotherapy treatment with combination of 5-fluorouracil and leucovorin or interferon alpha determined an incidence of severe diarrhoea of 10 and 20%, respectively. Up to date no treatment for this condition has been defined. 21 patients affected by advanced colorectal cancer and 6 patients affected by advanced pancreatic cancer received octreotide as treatment for severe diarrhoea following chemotherapy with 5-fluorouracil/leucovorin (Machovers regimen) or 5-fluorouracil/interferon (Wadlers regimen) combination. Octreotide was administered by subcutaneous injection of 50 micrograms twice daily on the first day and 100 micrograms twice daily on the second and third day. 26 patients had total cessation of diarrhoea: 4 patients within the first day, 6 within the second day and 16 within the third day. 1 patient had no change and after the last administration of octreotide he was treated with loperamide and intravenous hydration. Side effects have been mild. In summary octreotide seems to be an effective agent in the management of chemotherapy related diarrhoea.

HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer

Catalano V, Mellone P, d’Avino A, Shridhar V, Staccioli M P, Graziano F, Giordani P, Rossi D, Baldelli A M, Alessandroni P, Santini D, Lorenzon L, Testa E, D’Emidio S, De Nictolis M, Muretto P, Fedeli S L & Baldi A
(2011) Histopathology58, 669–678
HtrA1, a potential predictor of response to cisplatin‐based combination chemotherapy in gastric cancer

Neoadjuvant chemotherapy with low dose of pegylated liposomal doxorubicin plus weekly paclitaxel in operable and locally advanced breast cancer.

To determine the activity and safety of a schedule with a low dose of pegylated liposomal doxorubicin (PLD) and weekly paclitaxel in operable and locally advanced breast cancer patients. Thirty-five patients with histologically confirmed, operable, and locally advanced breast cancer entered the study. The median age was 59 years (range 31–74 years). The schedule was biweekly PLD at the dose of 15 mg/m2 for four administrations and weekly paclitaxel at the dose of 80 mg/m2 for eight administrations. All patients were evaluable for response and toxicity. Twenty-six patients responded (74%): three (8%) had a complete response and 23 (66%) had a partial response, seven (23%) remained stable, and one experienced progression (3%). Fifteen of 27 operable patients (55%) underwent conservative surgery. Three patients (9%) had a pathological complete response and the disappearance of infiltrating disease was documented in three other patients. The main toxicity was hand–foot syndrome (grade 3 in four patients; 11%). Other nonhematological grade 3 toxicities included stomatitis in three patients (8%) and liver toxicity in one patient (3%). Grade 3–4 neutropenia was documented in another three patients and dose reduction was necessary in two patients. The fourth administration of PLD was suspended in four patients for grade 2–3 hand–foot syndrome. No symptoms were related to impairment of cardiac function and no death related to toxicity occurred. The combination of biweekly PLD and weekly paclitaxel was active in operable and locally advanced breast cancer with a manageable safety profile.

Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

Background Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. Patients and methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05). Conclusions RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

Experience with intrapleural natural beta interferon in the treatment of malignant pleural effusions.

Malignant pleural effusion is a common complication of cancer. Intrapleural beta interferon has been recently tested, and responses were obtained in about 1/3 of the patients without considerable side effects. We treated 22 patients with recurrent symptomatic malignant pleural effusions with intrapleural beta interferon at increasing doses (5–15 million units) for a maximum of three courses and obtained only two responses. In our opinion, this schedule cannot be recommended for routine use.

Standard vs adapted sunitinib regimen in elderly patients with metastatic renal cell cancer: results from a large retrospective analysis.

BACKGROUND There are no data on the patterns of care and outcome of elderly patients with mRCC treated with sunitinib. In a retrospective study, we assessed the routine use of first-line sunitinib in mRCC patients aged ≥ 70 years. PATIENTS AND METHODS We reviewed the clinical files of 185 patients aged ≥ 70 years with mRCC treated with first-line sunitinib in 17 Italian oncology units from February 2006 to September 2011. One hundred twenty-three patients (66.5%) received a standard 50 mg/d for a 4 weeks on/2 weeks off regimen (SR), and 62 patients (33.5%) received an AR consisting of 37.5 mg/d for a 4 weeks on/2 weeks off in 67.7% of cases. RESULTS Median age was 74 years. Patients treated with an AR were older than those treated with the SR (P < .0001). In the overall population, the median progression-free survival (PFS) was 11 months, and the median overall survival (OS) was 25.5 months. Grade 3-4 toxicities occurred in 87 of 123 SR (70.7%) and 32 of 62 AR (51.6%), respectively; dose reductions were required in 82 SR (66.7%) and 26 AR (41.9%), respectively; discontinuations because of therapy-related adverse events occurred in 25 SR (20.3%) and 15 AR (24.2%), respectively. In multivariate analysis, only performance status and the Heng score were predictors of either PFS or OS. CONCLUSION Sunitinib is active and feasible in elderly patients with mRCC. A sunitinib AR could be considered as an option in selected older mRCC patients. The optimal treatment of frail patients with mRCC remains to be established.

Weekly docetaxel as second-line therapy in non-small cell lung cancer: a phase II study.

Introduction Single-agent docetaxel is active as second-line chemotherapy in non-small cell lung cancer (NSCLC) pretreated patients; seven phase II studies have shown response rates of about 20% and 9 months of median survival. Two phase III studies documented a survival benefit at 1 year compared to BSC and vinorelbine or ifosfamide. Recent trials indicate acceptable activity and a good safety profile of weekly docetaxel with doses of 25–43 mg/m2. The aim of our study was to confirm this evidence and to evaluate activity and toxicity of weekly docetaxel at the dose of 40 mg/m2. Patients and methods Twenty-one patients with NSCLC entered the study (7 stage NIB and 14 stage IV): 13 males and 8 females. Median age was 66 years (range, 53–75). ECOG was O in 6, 1 in 9 and 2 in 6 patients. All patients were pretreated with a first-line chemotherapy (13 patients progressed soon after the first line); 6 of them received palliative radiotherapy on the chest. The treatment consisted of weekly docetaxel, 40 mg/m2 in 1 hr for six weeks with two weeks of rest (1 cycle). A total of 87 administrations was delivered (median, 4; range, 1–12). Responses All patients were assessable for response (according to the “intent-to-treat principle”) and for toxicity. No complete or partial remission was observed; 2 minor responses (9.5%), 1 stable disease (5%), 8 progressive diseases (38%) were documented. Seven patients dropped out the study due to severe toxicity (33.5%) and 3 due to early death (14%). Median survival was 3 months (range, 1–17), and 1-year survival was 9.5%. Toxicity was as follows: grade 4 diarrhea in 1; grade 3 asthenia in 8 (38%), grade 3 stomatitis in 2; grade 3 neutropenia in 1; allergic reactions in 2. No treatment-related death was recorded. Conclusions The trial showed only very modest activity of weekly docetaxel, with severe side effects that induced us to stop the accrual in order to prevent other worse toxicities. We therefore concluded that a dose of 40 mg/m2 of weekly docetaxel is not manageable and does not seem to provide a real benefit in terms of response and quality of life.

Sunitinib as first-line therapy in elderly patients (age 70 and older) with metastatic renal cell cancer.

411 Background: Many medical oncologists are still reluctant to use the standard sunitinib regimen in older patients (pts) with metastatic renal cell cancer (mRCC) because of concerns about tolerance. We assessed the routine use of first-line sunitinib in mRCC pts aged ≥70 yrs. METHODS We reviewed the clinical files of 154 pts aged ≥70 yrs with mRCC treated with first-line sunitinib in sixteen Italian Oncology Units from February 2006 to April 2011. Sunitinib 50 mg/d 4 wk on/2 wk off was considered the standard regimen (SR). All alternative schedules of sunitinib administration were considered as adapted regimens (AR). After univariate analysis a multivariate analysis was carried out by Cox regression model and included the following variables: age (<75 vs ≥75 yrs), Eastern Cooperative Oncology Group (ECOG) performance status (PS; 0-1 vs ≥2), presence of comorbidities (0 vs ≥1), lymphocytopenia (<1,000/microL vs >1,000/microL), prognostic score for VEGF-targeted agents according to Heng 2009 (good + intermediate prognosis vs poor prognosis), and treatment schedule (SR vs AR). RESULTS Median age was 74 yrs (range, 70-88 yrs). One hundred six pts (68.8%) received a SR and 48 (31.2%) received an AR consisting of 37.5 mg/d 4 wk on/2 wk off (32 cases, 67%), 25 mg/d 4 wk on/2 wk off (12 cases, 25%) and 37.5 mg continuous once-daily dosing in (4 cases, 8%). Pts treated with an AR were older than those treated with the SR (≥75 yrs, 56% vs 32%, respectively, p=0.008); with no differences for the other variables. Pts received a median of 4 sunitinib cycles with either SR or AR. Grade 3-4 toxicities occurred in 65% of SR and 42% of AR (p=0.008); dose reductions were required in 64% and 40%, respectively (p=0.005); discontinuations due to therapy-related adverse events occurred in 23% and 21%, respectively (p=0.967). Median progression-free survival (PFS) was 10.6 months (95% CI 8.7-15.3) and median overall survival (OS) was 20.1 months (95% CI 15.5-not reached). In multivariate analysis, only PS and the Heng score were predictors of either PFS or OS. CONCLUSIONS Sunitinib is active and feasible in pts with mRCC aged ≥70 yrs. AR does not appear to influence PFS and OS and has a favorable impact on toxicity.