A prospective phase II study of topotecan (Hycamtin®) and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer.

OBJECTIVES: To evaluate the feasibility, toxicity and activity of neoadjuvant chemotherapy (NACT) using cisplatin and topotecan in patients affected by locally advanced cervical cancer (IB2-IIIB). METHODS: Patients with histologically confirmed FIGO stage IB2-IIIB uterine cervical cancer were treated with topotecan 0.75 mg/m(2)/day (days 1-3) followed by cisplatin 75 mg/m(2) (day 1), every 21 days for three consecutive cycles. After the last cycle of chemotherapy, within 3 or 4 weeks, patients underwent radical surgery with lymph node dissection. RESULTS: In the years 2007-2010, 46 women were enrolled into the study. Hematologic toxicity was the most relevant side effect. Thirty-eight patients (82.6%) underwent radical surgery after neoadjuvant chemotherapy (NACT) and were assessable for pathologic responses; surgery was not performed in 8 (17.4%) non-responder patients or with progression disease. Objective pathological response was recorded in 34 patients (89.5%); 6 patients (15.8%) achieved a complete response (CR), 28 (73.7%) patients achieved a partial response (PR); stable disease (SD) occurred in 2 patients (5.3%) with IIA initial disease and progression disease (PD) was registered in 2 patients (5.3%) with IIIB initial disease. The cumulative 2-year progression free survival (PFS) and overall survival (OS) of the 46 enrolled patients in the study were 70% and 81%, respectively; the 2-year PFS and OS of the 38 operated patients were respectively 79% and 95%. CONCLUSIONS: The cisplatin-topotecan combination seems to be feasible and with an acceptable toxicity profile and a promising response rate for the treatment of locally advanced cervical cancer (LACC). Phase II and III studies are needed to compare this combination with other platinum-based chemotherapeutic associations.

Bulky lymph node resection in patients with recurrent epithelial ovarian cancer: impact of surgery.

The aim of this study was to evaluate the role of systematic lymphadenectomy, feasibility, complications rate, and outcome in epithelial ovarian cancer (EOC) patients with recurrent bulky lymph node disease. A prospective observational study of EOC patients with pelvic/aortic lymph node relapse was conducted between January 1995 and June 2005. After a clinical and laparoscopic staging, secondary cytoreduction, including systematic lymphadenectomy, were performed. The eligibility criteria were as follows: disease-free interval > or =6 months, radiographic finding suggestive of bulky lymph node recurrence, and patients' consent to be treated with chemotherapy. Forty-eight EOC patients with lymph node relapse were recruited. Twenty-nine patients were amenable to cytoreductive surgery. Postoperatively, all patients received adjuvant treatment. The median numbers of resected aortic and pelvic nodes were 15 (2-32) and 17 (8-47), respectively. The median numbers of resected aortic and pelvic positive lymph nodes were 4 (1-18) and 3 (1-17), respectively. The mean size of bulky nodes was 3.3 cm. Four patients (14%) experienced one severe complication. No treatment-related deaths were observed. After a median follow-up of 26 months, among cytoreduced patients, 18 women were alive with no evidence of disease, nine were alive with disease. Among the 11 patients not amenable to surgery, five women were alive with persistent disease, six patients died of disease, at a median follow-up of 18 months. Estimated 5-year overall survival and disease-free interval for operated women were 87% and 31%, respectively. In conclusion, patients with bulky lymph node relapse can benefit from systematic lymphadenectomy in terms of survival. The procedure is feasible with an acceptable morbidity rate.

Hemoglobin variation and blood transfusion rates in patients affected by locally advanced cervical cancer undergoing neo-adjuvant chemotherapy followed by radical surgery: the role of erythropoietic growth factors.

BACKGROUND: The objectives of the present study were to evaluate hemoglobin levels and consequent clinical behaviors related to anemia developed in patients affected by locally advanced cervical cancer treated with neo-adjuvant chemotherapy in the last decade and to evaluate the impact that the introduction of erythropoietic growth factors had in the clinical practice. PATIENTS AND METHODS: Blood chemistries, prospectively recorded from 98 cervical cancer patients, treated with neo-adjuvant chemotherapy and, if necessary, erythropoietic growth factors, were compared with matched historical controls before the introduction of growth factors in clinical practice. RESULTS: Hemoglobin level in the study group did not differ significantly during chemotherapy. At the third cycle of chemotherapy and at the end of chemotherapy, hemoglobin level was significantly higher in the study group compared with the control group. Transfusion rates in the study group were significantly lower. The analysis within the study group revealed that hemoglobin level in patients who suffer at diagnosis from anemia tends to increase whereas hemoglobin level in nonanemic patients tends to decrease. CONCLUSIONS: Erythropoietic growth factors increase hemoglobin level and reduce blood transfusions in cervical cancer patients undergoing neo-adjuvant chemotherapy followed by radical surgery. An appropriate autologous blood donation program can noticeably reduce homologous blood transfusions.

Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies.

The aim of this study was to evaluate the safety and efficacy of liposome-encapsulated doxorubicin citrate (LEDC) in patients affected by recurrent/metastatic gynecological malignancies scheduled for palliative chemotherapy. Inclusion criteria were proven recurrent/advanced gynecological neoplasms, measurable/assessable disease, adequate organ function, left ventricular ejection fraction >50% as determined by echocardiography, informed consent. LEDC was administered intravenously over 1 h at the dose of either 75 mg/m(2) or 60 mg/m(2) (every 3 weeks until disease progression or toxicity prohibiting further therapy). From May 2003 to September 2005, 36 patients were enrolled. Primary disease was ovarian, endometrial, and cervical cancers in 15 (42%), 11 (30%), and 10 (28%) patients, respectively. LEDC was employed as third- or fourth-line chemotherapy in 25 (70%) and 11 (30%) patients, respectively. The median number of courses of LEDC received was 3 (range 2-9). Six patients (17%) achieved a partial response to treatment lasting 27 weeks and 10 patients (28%) experienced stable disease lasting 18 weeks. The predominant toxicity was hematological, especially neutropenia. Among patients receiving a dose of 75 mg/m(2), two (11%) suspended therapy for febrile neutropenia, and nine (50%) required a dose reduction of 25%. As a result, the next 18 patients were treated at a reduced dose (60 mg/m(2)) of LEDC. Severe neutropenia (G3-G4) was significantly less common in this group (61% versus 22%; P= 0.04). LEDC has shown antineoplastic activity in previously treated recurrent/metastatic gynecological cancer patients and the toxicity profile could be considered acceptable at a 60 mg/m(2) dosage.

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

Gynecological cancers in developing countries: the challenge of chemotherapy in low-resources setting.

The epidemiologic pattern of cancers in developing countries differs in many aspects from that of industrialized nations. Cancer natural history, microbiologic environment, patient's immune system, and drug availability may differ as well. Four of five new cases of cervical cancer and most of cervical cancer deaths occur in developing countries. Where chemoradiation and supportive care facilities are unavailable, it would be logical to consider an inexpensive effective drug. In locally advanced cases, neoadjuvant chemotherapy followed by surgery should be considered the treatment of choice. For ovarian cancer, it may be reasonable to maintain a secure supply of platinum and/or taxanes. For endometrial cancer, platinum compounds are proved active chemotherapic single agents. Oral medroxyprogesterone acetate (MPA) may represent a good chance for treating an advanced or recurrent disease. For vulvar/vaginal cancer, the role of chemotherapy alone is currently considered limited, and it is mostly used as palliative treatment in advanced or recurrent cases. Whenever possible, standard western chemotherapic regimens should be applied in developing countries as well. When standard therapies are unavailable, drugs of choice should be easily accessible, inexpensive, and effective. The most commonly used drugs are cisplatin, cyclophosphamide, and MPA.

The role of neoadjuvant chemotherapy followed by radical surgery in the treatment of locally advanced cervical cancer.

In 1984 the first pilot study on neoadjuvant chemotherapy in cervical cancer was reported. Since then, many investigators have studied the possible role that this therapeutic strategy could achieve in patients. Different chemotherapic combinations are constantly being attempted in order to obtain the maximum tumour response. At the same time few randomised studies have demonstrated the superiority of this treatment when adopted before radical surgery, in terms of overall survival compared to radiotherapy alone. Recently a detailed meta-analysis has been performed and the results confirmed what previously was achieved by the randomised trials. Since the beginning of all the phase III trials, the standard treatment of locally advanced disease has been modified from radiotherapy alone to concomitant radio-chemotherapy. For this reason the EORTC group has launched a trial with the objective of comparing neoadjuvant chemotherapy followed by radical surgery versus concomitant chemo-radiotherapy.

Pure Leydig cell tumour (hilus cell) of the ovary: a rare cause of virilization after menopause.

A 58-year-old postmenopausal woman with high plasma testosterone levels and virilization, as demonstrated by hirsutism and alopecia, is presented. Urinary 17-ketosteroids and 17-hydroxycorticosteroids as well as the computed axial tomography scan of the adrenal glands were normal. Although no pelvic mass was detected by sonography or pelvic examination, the patient was found to have small pure Leydig cell tumour of the left ovary. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the patient had regression of the hirsutism, and the plasma testosterone dropped to normal level.