Impact of age and gender on the efficacy and safety of upfront therapy with panitumumab plus FOLFOX followed by panitumumab-based maintenance: a pre-specified subgroup analysis of the Valentino study.

BACKGROUND: The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored. PATIENTS AND METHODS: Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). RESULTS: No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or ≥70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients. CONCLUSIONS: The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted.

A prognostic model based on combining estrogen receptor expression and Ki-67 value after neoadjuvant chemotherapy predicts clinical outcome in locally advanced breast cancer: extension and analysis of a previously reported cohort of patients.

BACKGROUND: Ki-67 expression has gained attention as a breast cancer prognostic factor, however its significance in the remaining malignant cells after neoadjuvant chemotherapy (NAC) has been rarely examined. This investigation, extension and analysis of a previously reported cohort of patients, evaluates the significance of Ki-67 and estrogen receptor (ER) expression after NAC in LABC (locally advanced breast cancer). PATIENTS AND METHODS: clinical stage, tumor size, clinical and pathological lymph node involvement, Ki-67, ER, progesterone receptor (PgR), HER2 expression, grading and clinical response were evaluated before and after NAC in 110 patients with LABC. Ki-67 expression was assessed both in pre and post-therapy histological samples, using >15% positive cells as cut-off value to distinguish high from low Ki-67 expressing tumors. RESULTS: six patients (5.45%) attained pCR after NAC. A significant relationship between elevated post-CT Ki-67 and ER expression was showed at Cox multivariate analysis of disease free survival (DFS). On univariate analysis high post-chemotherapy Ki-67 and ER status were associated with worse survival; at multivariate model included these results were confirmed. Based on these two parameters, a prognostic model identified two different groups: low risk (low postchemotherapy Ki-67 and ER positive, or either high post-chemotherapy Ki-67 or ER negative), and high risk (high post-chemotherapy Ki-67 and ER negative). The low risk group showed a good prognosis (median OS still not reached), while the high risk group had a worse OS (median 41 months). CONCLUSIONS: Ki-67 value after NAC and ER status could predict a worse prognosis among LABC patients treated with NAC.

Bi-weekly docetaxel and gemcitabine regimen in her-2-negative and anthracycline-pretreated metastatic breast cancer patients: a multicenter phase II trial.

PURPOSE: Bi-weekly gemcitabine (G) in combination with docetaxel (D) is an effective treatment for metastatic breast cancer (MBC) previously treated with adjuvant/neoadjuvant anthracyclines containing regimens with a good toxicity profile. In the present phase II study, we investigated the activity of the same regimen as first-line treatment. METHODS: Women with breast cancer pretreated in adjuvant/neoadjuvant setting with anthracyclines received bi-weekly G (1,250 mg/m² days 1, 15) and D (50 mg/m² days 1, 15) every 28 days with restaging after 3 and 6 cycles. RESULTS: Overall 42 patients were enrolled. Median age is 48 years (range, 31-71 years). Eight patients (19%) achieved complete responses, 18 (43%) partial responses for an overall response rate (ORR) of 62%; five patients (12%) obtained stable disease (SD), and 8 (19%) patients had progressive disease (PD). After a median 17-month follow-up, the median time to disease progression was 12 months (95% CI, 3-26 months) and the median survival time was 27 months (95% CI, 4-57 months). No grade 4 toxicity was seen except in one patient who developed a grade 4 neutropenia. Grade 3 toxicities were leukopenia (2%), neutropenia (14%), anemia (2%), nausea and vomiting (2%), diarrhea (2%), asthenia (2%), and skin toxicity (12%). CONCLUSION: The GD bi-weekly regimen is well tolerated and active as first line in anthracyclines-pretreated women with MBC. It appears as an interesting alternative compared to a 3-week schedule whenever hematological toxicity is the main clinical concern.

Leiomyosarcoma of the broad ligament: a case report and review of literature.

Leiomyosarcoma of the broad ligament is a rare tumor, since only 12 cases have been reported so far in the literature. A 53-year-old patient was diagnosed with leiomyosarcoma of the broad ligament at the Department of Gynecology Oncology of the National Cancer Research Institute in Genoa. The tumor had low mitotic activity and less than ten mitotic figures were found for ten high-power fields. The treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with bilateral ureteral neoanastomosis and omentectomy. The patient has not received either radiotherapy or chemotherapy, considering the low grade of malignancy, but she is only followed up on an outpatient basis. No evidence of metastasis has been noted after a follow-up of 13 months. It is concluded that low-grade leiomyosarcoma of the broad ligament should be treated only with surgery.

Serum enterolactone levels and the risk of breast cancer in women with palpable cysts.

Low levels of lignans, namely enterolactone, have been reported to be associated with an increased risk of breast cancer in the general female population. We assessed, retrospectively, the relationship between serum enterolactone concentrations and the occurrence of breast cancer in women with palpable cysts. The levels of enterolactone in cryopreserved serum aliquots, obtained from 383 women with palpable cysts at the time of their first cyst aspiration, were measured using a time-resolved fluoroimmunoassay (TR-FIA). After a median follow-up time of 6.5 years (range 0.5-12.75 years), 18 women were found to have developed an invasive breast cancer. Median values of serum enterolactone were significantly lower in women who subsequently developed breast cancer: 8.5 nM/l versus 16.0 nM/l: P=0.04. Odd Ratios (OR) for breast cancer were: 0.36 (P=0.03), 0.57 (P=0.3) and 0.38 (P=0.25) for 25th (8 nM/l), 50th (16 nM/l) and 75th (24 nM/l) percentile values, respectively. The receiver operating characteristic (ROC) analysis showed a satisfactory accuracy for enterolactone as a breast cancer risk indicator (area under the curve (AUC)=0.64: P=0.04). Logistic regression analysis confirmed that the enterolactone concentration had a strong protective effect on the breast cancer risk. These findings may have important clinical implications with regard to interventional diet-focused chemo-preventive trials.