Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial.

PURPOSE: To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. METHODS: CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. RESULTS: Seventy-two out of 126 randomized patients were evaluated: 57% had ≥ 1 IGF-1R positive CTC and 37.5% ≥ 4 IGF-1R negative cells; 42% had CTC count ≥ 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. CONCLUSION: Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26).

Acupuncture As an Integrative Approach for the Treatment of Hot Flashes in Women With Breast Cancer: A Prospective Multicenter Randomized Controlled Trial (AcCliMaT).

PURPOSE: To determine the effectiveness of acupuncture for the management of hot flashes in women with breast cancer. PATIENTS AND METHODS: We conducted a pragmatic, randomized controlled trial comparing acupuncture plus enhanced self-care versus enhanced self-care alone. A total of 190 women with breast cancer were randomly assigned. Random assignment was performed with stratification for hormonal therapy; the allocation ratio was 1:1. Both groups received a booklet with information about climacteric syndrome and its management to be followed for at least 12 weeks. In addition, the acupuncture group received 10 traditional acupuncture treatment sessions involving needling of predefined acupoints. The primary outcome was hot flash score at the end of treatment (week 12), calculated as the frequency multiplied by the average severity of hot flashes. The secondary outcomes were climacteric symptoms and quality of life, measured by the Greene Climacteric and Menopause Quality of Life scales. Health outcomes were measured for up to 6 months after treatment. Expectation and satisfaction of treatment effect and safety were also evaluated. We used intention-to-treat analyses. RESULTS: Of the participants, 105 were randomly assigned to enhanced self-care and 85 to acupuncture plus enhanced self-care. Acupuncture plus enhanced self-care was associated with a significantly lower hot flash score than enhanced self-care at the end of treatment (P < .001) and at 3- and 6-month post-treatment follow-up visits (P = .0028 and .001, respectively). Acupuncture was also associated with fewer climacteric symptoms and higher quality of life in the vasomotor, physical, and psychosocial dimensions (P < .05). CONCLUSION: Acupuncture in association with enhanced self-care is an effective integrative intervention for managing hot flashes and improving quality of life in women with breast cancer.

Increased mean corpuscular volume of red blood cells in patients treated with capecitabine for advanced breast and colon cancer.

PURPOSE: Capecitabine has demonstrated significant activity in metastatic breast and colorectal cancer. During the course of treatment with capecitabine, we observed that a relevant number of patients developed elevated levels of the mean corpuscular volume (MCV) of red blood cells. METHODS: This retrospective analysis reviewed treatment with capecitabine in 35 patients with histologically proven advanced breast and colon cancer. After 9 weeks of treatment, restaging was performed using the criteria proposed by the Committee of the Response Evaluation Criteria in Solid Tumours. RESULTS: Prior to the first cycle of capecitabine treatment, there were no abnormalities in red blood cells, white blood cells, haemoglobin or platelets. The median haemoglobin level prior to the first cycle was 13 g/dl and the MCV (normal range 80-98 fl) was 86.5 fl in colon cancer patients and 12.8 g/dl and 88.7 fl in breast cancer patients, respectively. During the course of treatment, 12 weeks after the baseline evaluation, an increase in MCV was documented, while haemoglobin levels remained stable. An MCV increase was documented between baseline and the end of treatment. We noticed an increase in MCV at the end of treatment both in patients with stable disease or a partial response (n = 17) compared to patients with tumour progression (n = 11) at the first evaluation (12-14 weeks). DISCUSSION: Preliminary results showed that there is a significant MCV increase in patients receiving capecitabine for metastatic colon and breast cancer after 12 weeks of treatment. However, when we compared the MCV rise after 12 weeks that occurred with stable disease or a partial response compared to that in patients with disease progression at the first evaluation, the analysis was not statistically significant.

Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial.

PURPOSE: Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS. RESULTS: Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles. CONCLUSION: Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.

A phase II study of capecitabine in the treatment of ovarian cancer resistant or refractory to platinum therapy: a multicentre Italian trial in ovarian cancer (MITO-6) trial.

PURPOSE: Capecitabine is an oral chemotherapeutic agent, already used in breast and colon cancer. Previous data showed encouraging results in the treatment of recurrent ovarian cancer. The aim of this study was to describe activity and toxicity of capecitabine in patients with platinum resistant or refractory ovarian cancer. METHODS: Patients were eligible if they had cytologically or histologically proven epithelial ovarian cancer, refractory or resistant to prior platinum-containing chemotherapy. Capecitabine was administered at the dose of 1,250 mg/m(2) twice daily on days 1-14 of a 21-day cycle for a maximum of six cycles. The primary end point of the study was activity in terms of objective response rate in according to RECIST criteria. A two-stage minimax design for phase II studies was used: at least four objective responses had to be reached among 32 evaluable patients to define the treatment active. RESULTS: Between March 2006 and October 2007, 36 patients were enrolled. All patients had ovarian cancer and 83.3% had previously received two or three lines of chemotherapy. Thirty-two patients were evaluable for response and included in the activity analysis. The objective response rate was 3.1% [95% exact confidence interval (CI): 0.08-16.22%], lower than the threshold required to define the treatment as active. The median progression free survival was 68 days (95% CI: 65-120). Haematological toxicity was not frequent. Nausea and fatigue were common, but never severe, and they were observed in 13 (37.1%) and 12 (34.2%) patients, respectively. Diarrhoea occurred in 11 patients (31.5%) and it was of grade 3 in 8.6% of cases. Grade 1-2 stomatitis was observed in seven patients (20%). Cardiovascular toxicity was reported in two cases, including a death for pulmonary embolism. CONCLUSIONS: Capecitabine is not active in platinum resistant non mucinous ovarian cancer, producing a response rate lower than that required by study design. Further trials are not warranted in these patients.

Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer.

PURPOSE: We aimed at investigating the efficacy, tolerability, and quality of life (QOL) of gemcitabine (GEM) compared with pegylated liposomal doxorubicin (PLD) in the salvage treatment of recurrent ovarian cancer. PATIENTS AND METHODS: A phase III randomized multicenter trial was planned to compare GEM (1,000 mg/m(2) on days 1, 8, and 15 every 28 days) with PLD (40 mg/m(2) every 28 days) in ovarian cancer patients who experienced treatment failure with only one platinum/paclitaxel regimen and who experienced recurrence or progression within 12 months after completion of primary treatment. RESULTS: One hundred fifty-three patients were randomly assigned to PLD (n = 76) or GEM (n = 77). Treatment arms were well balanced for clinicopathologic characteristics. Grade 3 or 4 neutropenia was more frequent in GEM-treated patients versus PLD-treated patients (P = .007). Grade 3 or 4 palmar-plantar erythrodysesthesia was documented in a higher proportion of PLD patients (6%) versus GEM patients (0%; P = .061). The overall response rate was 16% in the PLD arm compared with 29% in the GEM arm (P = .056). No statistically significant difference in time to progression (TTP) curves according to treatment allocation was documented (P = .411). However, a trend for more favorable overall survival was documented in the PLD arm compared with the GEM arm, although the P value was of borderline statistical significance (P = .048). Statistically significantly higher global QOL scores were found in PLD-treated patients at the first and second postbaseline QOL assessments. CONCLUSION: GEM does not provide an advantage compared with PLD in terms of TTP in ovarian cancer patients who experience recurrence within 12 months after primary treatment but should be considered in the spectrum of drugs to be possibly used in the salvage setting.

Single-agent gemcitabine in previously untreated elderly patients with advanced bladder carcinoma: response to treatment and correlation with the comprehensive geriatric assessment.

OBJECTIVE: The study aimed at evaluating the activity and toxicity of gemcitabine monochemotherapy in a unselected series of elderly patients with advanced bladder cancer. The secondary objectives were to establish whether there is a correlation between treatment and Comprehensive Geriatric Assessment (CGA) and, in addition, to determine overall patient survival. METHODS: Treatment consisted of six courses of chemotherapy with gemcitabine at a dosage of 1,200 mg/m2 on days 1 and 8, every 21 days. CGA, as described by Gruppo Italiano di Oncologia Geriatrica, was assessed for evaluating the functional status of patients before, during, and after treatment. RESULTS: Twenty-five patients were enrolled (M/F 22/3), 22 of these were evaluable for response and 23 for toxicity. Characteristics of patients: median age 76 years (range 71-87); ECOG performance status (PS) 1 in 12 patients and 2 in 13 patients; clinical stage III in 6 patients and IV in 19 patients. At the end of the therapy the parameters of CGA improved in 4 cases (17%), remained unchanged in 17 cases (74%) and worsened only in 2 cases (9%). Two patients were not evaluable. Response evaluation showed 3 (13.5%) complete responses (CRs) and 7 (32%) partial responses (PRs), for an overall response rate of 45.5% [95% confidence interval (CI), 24.3-65.7%]. Three (13.5%) patients had stable disease (SD ) and 9 (41%) disease progression (DP). Median overall survival was 8 months and median time to progression was 5 months. Treatment was generally well tolerated, with 1 patient having grade 3 gastrointestinal toxicity and 3 having grade 4 neutropenia. CONCLUSIONS: We conclude that gemcitabine can be safely administered in monochemotherapy, is effective and does not worsen the functional status of elderly patients with advanced bladder cancer.