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Biomedical subjects

Andrea Rocca

Publications and source records attributed to Andrea Rocca.

11 recordsLinked to original sources
PubMed2006

Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic breast cancer.

BACKGROUND: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We therefore tested the activity of the combination of Trastuzumab with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and methotrexate (MTX) in metastatic breast cancer (MBC). METHODS: Between April 2002 and June 2005, twenty-two patients with metastatic breast cancer with the presence of overexpression or amplification of HER2-/neu, all pre-treated with trastuzumab plus other cytotoxics, were treated with trastuzumab (6 mg/kg every three weeks) in combination with metronomic chemotherapy (MTX 2.5 mg, bid on Day 1 and Day 4 every week) and CTX (50 mg daily) (CM). RESULTS: The 22 enrolled patients are evaluable: most had an ECOG performance status of 0 (17 pts), and all were pre-treated with chemotherapy for metastatic disease; 14 had progressive disease at study entry, and 11 had progressive disease during the last trastuzumab therapy. Metastatic sites included: lung (5 pts), liver (14 pts), bone (12 pts), lymph nodes (8 pts), central nervous system (CNS) (9 pts). We observed 4 partial remission (PR) (18%, 95% CI 5-40%), 10 stable disease (SD) (46%, 95% CI 24-68%), and 8 PD (36%, CI 17-59%). The clinical benefit (RP plus RC plus SD for > or = 24 weeks) in all pts and in pts with disease resistant to previous trastuzumab therapy were 46% (95% CI, 24-68%) and 27% (95% CI, 6-61%), respectively. Median time to progression was 6 months and median duration of treatment was 5 months (range, 0,7 to 18.4 months and range, 1 to 18 months, respectively). Overall clinical toxicity was generally mild. Grade > or =2 reversible liver toxicity and leukopenia were reported in 5 and 3 pts, respectively. CONCLUSION: The combination of trastuzumab and metronomic chemotherapy is effective and minimally toxic in advanced breast cancer patients. The efficacy observed in patients with disease resistant to trastuzumab supports the need of larger trial to confirm a role of this combination to delay acquired trastuzumab resistance.

Adult↗
PubMed2006

Primary therapy with ECF in combination with a GnRH analog in premenopausal women with hormone receptor-positive T2-T4 breast cancer.

Patients with hormone receptor-positive tumors less often show a pathological complete response (pCR) than do those with hormone receptor-negative tumors. The addition of endocrine therapies may improve the clinical benefits of primary therapies in these patients. We investigated the efficacy of the epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in association with a gonadotropin-releasing hormone (GnRH) analog in 36 premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer. Median age was 39.5 years (range 26-53). Clinical response (complete or partial) was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was observed in four patients (11%). Nine (25%) patients had stable disease and no progression was observed. Twenty-one patients (58%) were submitted for breast-conserving surgery and 15 had a radical mastectomy. No baseline clinical and biological characteristics significantly correlated with response. Thirty out of 31 patients evaluable for endocrine assessment had documented ovarian suppression, which occurred after a median of 28 days (range 20-43). We conclude that the combination of ECF and a GnRH analog is associated with a high response rate in the primary treatment of breast cancer. Further studies combining chemotherapy and endocrine agents are warranted in patients with hormone receptor-positive tumors.

Adult↗
PubMed2006

Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer.

The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cyclophosphamide (CTX) and methotrexate (MTX) (CM) have been demonstrated. The authors report results and long-term follow-up for patients with metastatic breast carcinoma who obtained prolonged clinical benefit with CM. Prospectively collected data from two successive clinical trials were evaluated. From July 1997 to October 2003, patients with metastatic breast carcinoma were treated with low-dose oral chemotherapy (MTX 2.5 mg, twice daily on day 1 and day 2 or 4, and CTX 50 mg daily). Patients who achieved prolonged clinical benefit for a duration of 12 months or more (complete remission, partial remission or stabilization of disease) were considered for the analysis. Median follow-up was 23 months. A total of 153 patients were enrolled and are evaluable: Eastern Cooperative Oncology Group performance status 0-1 in 90 patients, two or more sites of metastatic disease in 97 patients, zero regimen for metastatic breast carcinoma in 48 patients. Among 153 patients, five demonstrated complete remission and 25 partial remission. The proportion of patients who achieved prolonged clinical benefit was 15.7% (95% confidence interval 9.9-21.4%). Median time to progression for patients with prolonged clinical benefit was 21 months (range 12-37+ months). One patient maintained complete remission 42 months after therapy discontinuation. At the multivariate analysis endocrine responsiveness and the achievement of an objective response significantly correlated with the achievement of prolonged clinical benefit. Metronomic chemotherapy can induce prolonged clinical benefit in metastatic breast cancer, supporting its role as an additional therapeutic tool in the treatment of patients with metastatic breast carcinoma.

Administration, Oral↗
PubMed2006

A randomized phase II trial comparing preoperative plus perioperative chemotherapy with preoperative chemotherapy in patients with locally advanced breast cancer.

The aim of this study was to investigate in a randomized trial the activity of perioperative chemotherapy in patients treated with preoperative chemotherapy for locally advanced breast cancer and to compare it with the preoperative chemotherapy alone. Patients with cT2-3 N0-2 M0 histologically proven breast cancer, with estrogen receptors and progesterone receptors in less than 20% of cells, or with absence of progesterone receptors, received epirubicin 25 mg/m days 1 and 2, cisplatin 60 mg/m day 1, and fluorouracil 200 mg/m daily as continuous infusion. Responding patients were randomized to continue fluorouracil until 2 weeks after surgery (perioperative chemotherapy) or to stop fluorouracil 1 week before surgery. Fifty-eight patients completed six courses of epirubicin, cisplatin and fluorouracil, and were randomized to perioperative chemotherapy (29 patients) or to control (29 patients). The median Ki-67 index remained stable (32-27.5%) in the perioperative chemotherapy arm (P=0.3) and decreased from 55 to 22.5% in the control arm (P=0.01). The rate of pathological complete remission was 41% in both arms (P=1.0). No significant difference in terms of disease-free survival and overall survival was observed between the two arms. Perioperative chemotherapy failed to show an increase in the pathological complete remission rate. A biological effect on Ki-67 expression was demonstrated.

Adult↗
PubMed2006

Capecitabine/vinorelbine: an effective and well-tolerated regimen for women with pretreated advanced-stage breast cancer.

BACKGROUND: The combination of capecitabine and vinorelbine is a potentially valuable treatment regimen for patients with advanced-stage breast cancer. The drugs are easy to administer and do not cause significant alopecia. In order to identify the spectrum of toxicity of a regimen containing 2 drugs, we conducted an extended phase I study aimed at defining maximum tolerated doses, recommended doses, safety, and efficacy in patients with pretreated advanced-stage breast cancer. PATIENTS AND METHODS: Forty-nine patients with advanced-stage breast cancer were treated with escalating doses of oral capecitabine from 500 mg/m2 to 1375 mg/m2 twice daily on days 1-14 and escalating doses of vinorelbine from 12.5 mg/m2 to 25 mg/m2 intravenously (I.V.) on days 1 and 3 every 3 weeks. Almost all patients (90%) had received >or= 3 previous treatments for metastatic disease (anthracyclines, 76%; 5-flourouracil, 76%; taxanes, 29%). RESULTS: Dose level 9 (capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3) was identified as the maximum tolerated dose. The most frequent clinical adverse events were nausea (78%), asthenia (59%), constipation (51%), mucositis (47%), and hand-foot syndrome (41%). The majority of events were mild to moderate; the only grade 4 clinical adverse events were diarrhea, fever, and thromboembolism, each of which occurred in 1 patient (2%) at dose level 8. Objective confirmed responses were observed in 18 patients (37%), including 1 complete response (2%) and 17 partial responses (35%). Disease was stable in an additional 10 patients (20%), with a median duration of 6.3 months (range, 4-24 months). CONCLUSION: The combination of the 2 drugs is very well tolerated and effective, especially considering the previous exposure to chemotherapy. The recommended dose for further phase II studies should be capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3.

Adult↗
PubMed2005

Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy.

INTRODUCTION: The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer. METHODS: Ten patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER or PgR, were treated with weekly trastuzumab at standard doses with or without chemotherapy. RESULTS: Three out of 10 patients showed overexpression of ERs first appearing after 9, 12 and 37 weeks, respectively, from the initiation of trastuzumab. Two of these patients were subsequently treated with endocrine therapy alone: one of them received letrozole for 3 years without evidence of progression. CONCLUSION: Therapeutic targets enabling the appearance of an endocrine responsive disease may increase treatment options for patients with breast cancer. Furthermore, these clinical data suggest that an ER-negative phenotype is a multi-step process with a reversible repression modality, and that some ER-negative tumors may either revert to an ER-positive phenotype, allowing an endocrine treatment to be effective.

Antibodies, Monoclonal↗
PubMed2005

Perception that oral anticancer treatments are less efficacious: development of a questionnaire to assess the possible prejudices of patients with cancer.

We developed and pilot tested a 12-item questionnaire, to approach the issue of patients' perception on efficacy of oral chemotherapy. An additional question was on 'trade-off' between treatment efficacy and the ease of oral administration. The motivating underlying hypothesis was that oral drugs might be perceived by patients as less effective than when drugs were delivered by injection. The questionnaire was given to 59 patients with advanced breast cancer who received oral chemotherapy. Ninety-percent of patients considered clear and completed the questionnaire. Oral chemotherapy was positively viewed by most patients, perceiving it as advantageous (58%), able to help them feel less ill (77%) and to reduce the effort in coping with the disease (67%). The most important feeling elicited was the sense of freedom. Younger patients (<45 years) required bigger effort to face their illness and expected the most from oral chemotherapy. The questionnaire was shown to be robust, reliable and reproducible instrument in assessing patients' prejudices towards oral anticancer treatments.

Administration, Oral↗
PubMed2005

Update: current management issues in malignant melanoma.

The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.

Chemotherapy, Adjuvant↗
PubMed2004

Hyperfractionated radiotherapy in locally advanced nasopharyngeal cancer. An analysis of 43 consecutive patients.

BACKGROUND: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. PATIENTS AND METHODS: 43 patients with nasopharyngeal cancer (stage II-IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. RESULTS: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. CONCLUSION: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.

Adolescent↗
PubMed2002

Postoperative hyperprolactinemia could predict longer disease-free and overall survival in node-negative breast cancer patients.

OBJECTIVES: Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the clinical and biological impact of surgery-induced changes in PRL secretion still has to be clarified. The postoperative hyperprolactinemia has been related to aggressiveness of the tumor, early disease relapse or metastases, and poor overall survival in node-negative breast cancer patients. Surgery-induced hyperprolactinemia may be associated with a longer disease-free survival in both patients with or without node involvement. METHODS: One hundred twenty-seven consecutive node-negative breast cancer patients, who were hospitalized from June 1985 to September 1990, were included in this study. The median follow-up was 12 years. To evaluate PRL secretion, venous blood samples were obtained at day 7th after surgery. In order to exclude the influence of stress and gonadal status, GH and estradiol serum levels were measured in the same blood samples. All endocrine examination were made during the morning, starting at 8.00 a.m. after overnight fasting. Hormonal serum levels were determined by the double antibody radioimmunoassay method. RESULTS: Hyperprolactinemia was significantly more frequent in women younger than 50 years compared with the older ones, while the premenopausal status and T1 stage showed only a borderline significant association with hyperprolactinemia. Patients with normal postsurgical prolactinemia had 5- and 10-year disease-free survival rates of 64 and 56%, respectively, and 5- and 10-year overall survival rates of 84 and 70%, respectively. Patients with postsurgical hyperprolactinemia had 5- and 10-year disease-free survival rates of 89 and 81%, respectively, and 5- and 10-year overall survival rates of 94 and 81%, respectively. The difference in overall survival between the hyperprolactinemic and the normoprolactinemic groups, assessed by the log-rank test, was statistically significant (p = 0.02), and the difference in disease-free survival was highly significant (p = 0.0008). CONCLUSIONS: Our study shows that postsurgical hyperprolactinemia is associated with a significantly lower recurrence rate and longer disease-free and overall survival in operable node-negative breast cancer patients. Our data suggest that postoperative hyperprolactinemia could be crucial in the development of recurrence in operable breast cancer. Looking at results, the recurrence rate of node-negative patients who did not show postoperative hyperprolactinemia would be, in theory, similar to that of patients with node-positive disease, suggesting that normal postoperative PRL levels could identify a group of node-negative patients at high risk for recurrence.

Adult↗