C. Mendiola - Academia.edu (original) (raw)
Papers by C. Mendiola
Cancer Research, 2011
Purpose : Molecular classification of breast cancer (BC) through immunohistochemistry classifies ... more Purpose : Molecular classification of breast cancer (BC) through immunohistochemistry classifies patients globally in 4 subtypes with similar features and prognosis. The present study was designed to compare features of BC subtypes in early versus locally advanced clinical stages. A secondary objective was compare molecular subtypes of the primary vs recurrences. Methods : The study included 1621 patients with non-metastatic invasive BC that were consecutively diagnosed at Hospital Universitario 12 de Octubre, Madrid, between 1997 and 2007. Luminal A was defined as ER+ and PR+, HER2−negative and Ki67 < 14%. Luminal B was defined as PR-negative, HER2−positive or ki67≥14%. HER2 was defined as ER and PR-negative, and HER2−positive.Triple negative (TN) were tumors with ER, PR and HER2 -negativity. Clinicopathological characteristics and outcomes were retrospectively reviewed. Variables were compared with the X2 test, and survival curves were evaluated with Kaplan-Meier method. Result...
Clinical and Translational Oncology, 2013
In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GE... more In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GE-ICO), the first ''Treatment Guidelines in Ovarian Cancer'' were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308-316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750-755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript. Keywords Ovarian cancer Á Treatment guidelines Á Chemotherapy Á Surgery Á First line Á Recurrent disease Methodology During one and a half-day meeting, several topics on the management of ovarian cancer (OC) were reviewed by a panel of experts from GEICO about different areas. Each
Oncology, 2010
Aim: To retrospectively assess the efficacy and safety of bevacizumab plus low-dose metronomic or... more Aim: To retrospectively assess the efficacy and safety of bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Patients and Methods: Patients with recurrent ovarian cancer and prior treatment with platinum- and taxane-based chemotherapy were included. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks plus oral cyclophosphamide 50 mg daily until disease progression or unacceptable toxicity. Response rates (RR) were determined according to RECIST criteria and by monitoring the CA 125 serum tumor marker according to Rustin’s criteria. The endpoints were progression-free survival (PFS), RR, overall survival (OS), and safety. Results: Thirty-eight patients were treated; 79% were platinum resistant and 21% were platinum sensitive. The median number of previous treatments was 4 (range 1–8). Seventy-nine percent of patients had received more than 2 previous lines of treatment. Eighty-one percent of pat...
Journal of Clinical Oncology
16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and... more 16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and on disease-free survival (DFS) in patients with advanced cervical cancer receiving concurrent chemo-radiotherapy. Methods: One hundred thirty six patients with advanced cervical cancer (stage: 12 IB2-IIA, 34 IIB, 71 IIIB, 19 IVA); histology: 86 epidermoid and 14 adenocarcinoma) were analyzed to detect c-erbB-2 level using an immunohistochemical method (Herceptest Dako). Cases c-erbB-2 (+3) were considered positive. All patients received pelvic radiotherapy, brachitherapy and concurrent chemotherapy with two schedules: 48 patients with tegafur (800 mg/day via oral) and 88 with tegafur (same doses) plus five cycles of weekly cisplatin 40 mg/m2/week iv. Results: Of the 136 biopsies, 32 (23.5%) were c- erbB-2 positive. The disease free survival to 3 and 5 years of the patients were 61% and 58% for c-erb-B2 negative and 36% and 36% for c-erb- B2 positive (p=0.02), respectively.We divided our...
Clinical and Translational Oncology
An information under Table 2 was published incorrectly. The correct data should read as follows: ... more An information under Table 2 was published incorrectly. The correct data should read as follows: Visceral involvement No
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, Jan 24, 2017
This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estr... more This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.02...
Journal of Clinical Oncology
Journal of Clinical Oncology
Journal of Clinical Oncology
AIP Conference Proceedings, 2006
The impedance assessment to measure gastric emptying and in general gastric activity has been rep... more The impedance assessment to measure gastric emptying and in general gastric activity has been reported since 1985. The physiological interpretation of these measurements, is still under research. This technique usually uses a single frequency, and the conductivity parameter. The frequency domain and the Fourier analysis of the time domain behavior of the gastric impedance in different gastric conditions (fasting state,
Revista clínica española, Jan 15, 1979
British journal of cancer, Jan 6, 2006
To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin tar... more To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival w...
Seminars in oncology, 1995
From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung can... more From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for t...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 1994
From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution. Forty-three of t... more From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution. Forty-three of the pts were female (15.5%). Median age at diagnosis was 20 years (newborn-70). Histology was dysgerminoma (D) in 14 pts (including 2 anaplastic D), endodermal sinus tumor (EST) in 9 pts, immature teratoma in 10 pts and mixed tumors in 10 pts. Primary locations were as follows: ovary (O) 33 pts and extragonadal (EG) 10 pts (pineal in 4 cases, mediastinum in 3, sacrum in 2 and pharynx in 1). Stage: I in 20 (16 O, 4 EG), II in 7 (5 O, 2 EG), III in 12 (10 O, 2 EG) and IV in 4 (2 O, 2 EG). Serum AFP was elevated in 20/22 non-dysgerminoma pts, HCG in only 5 pts and LDH in 15/36 pts. Ovarian tumors: all but one pt (biopsy only) underwent surgery: unilateral oophorectomy was performed in 15 pts and bilateral oophorectomy (+/- hysterectomy, +/- others) in 17 pts. Fourteen pts were rendered disease-free, 8 pts had residual tumor (RT) < 2 cm and 11 RT > 2 cm. Chemotherapy (PVB or BEP) was gi...
The Lancet Oncology, 2011
Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and over... more Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive fi rst interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48•4 months (IQR 42•0-56•5) and assess the eff ect of the extensive crossover to trastuzumab. Our analysis was by intention-totreat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a signifi cant benefi t in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78•6%) compared with the observation group (4-year disease-free survival 72•2%; hazard ratio [HR] 0•76; 95% CI 0•66-0•87; p<0•0001). Intention-to-treat analysis of overall survival showed no signifi cant diff erence in the risk of death (4-year overall survival 89•3% vs 87•7%, respectively; HR 0•85; 95% CI 0•70-1•04; p=0•11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22•8 months (range 4•5-52•7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer diseasefree survival events than patients remaining in the observation group (adjusted HR 0•68; 95% CI 0•51-0•90; p=0•0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot fl ush, headache, and diarrhoea. Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with signifi cant clinical benefi t at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.
International Journal of Gynecological Cancer, 2010
To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relap... more To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relapse in patients with advanced cervical cancer (CC) receiving concurrent chemoradiotherapy treatment. A total of 136 patients with advanced CC (FIGO stage: IB2-IIA [12]; IIB [34]; IIIB [71]; IVA [19]; including both epidermoid [86] and adenocarcinoma [14]) were analyzed to determine c-erb-B2 levels by immunohistochemistry (c-erb-B2 antibody; Dako, Glostrup, Denmark). Only c-erb-B2+++ biopsies were considered positive. All patients received pelvic radiotherapy, brachytherapy, and concurrent chemotherapy with 2 different regimens: 48 patients were treated with tegafur (800 mg/d orally) and 88 with tegafur (same doses) plus 5 cycles of weekly cisplatin 40 mg/m/wk intravenously. A total of 32 (23.5%) biopsies were considered c-erb-B2-positive. Three-year and 5-year DFS were 61% and 58% for c-erb-B2-negative patients and 36% and 36% for c-erB2-positive patients, respectively (P = 0.02). Patients were stratified in 4 groups according to their c-erb-B2 status and whether they received cisplatin. The group of patients with c-erb-B2 overexpression that did not receive platinum treatment had a higher rate of pelvic relapse (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), associated with a decreased DFS (P = 0.0014). c-erb-B2 overexpression may imply a poor prognosis for patients with advanced CC. Treatment with cisplatin-based radiochemotherapy improved outcome in these patients.
European Journal of Cancer, 2003
Carcinosarcomas of the female genital tract are highly malignant tumours composed of carcinomatou... more Carcinosarcomas of the female genital tract are highly malignant tumours composed of carcinomatous and sarcomatous elements. In the past, these tumours were frequently treated as sarcomas. However, a number of arguments, including the sensitivity of these tumours to platinum-based chemotherapy, suggest that these tumours behave more like poorly differentiated carcinomas. The European Organization for Research and Treatment of Cancer (EORTC) Gynaecological Cancer Group therefore decided to perform a prospective phase II study in patients with advanced or metastatic carcinosarcoma with an approach such as that used in gynaecological carcinomas. Eligible patients could have primary or recurrent disease, but prior radiotherapy or chemotherapy was not allowed. The treatment plan recommended upfront debulking, followed by chemotherapy with cisplatin, ifosfamide and doxorubicin. Patients who could be debulked to non-measurable disease remained eligible for the study, but the response assessment was restricted to patients who had measurable disease before the start of chemotherapy. A total of 48 patients (39 primary disease, 9 recurrent disease) were registered, 41 of them being eligible. In 9 patients, all macroscopic lesions could be removed, 32 patients were left with residual disease and were assessable for response. The overall response rate was 56%: a complete response (CR) was observed in 11 (34%) patients and partial response (PR) in 7 (22%) patients. No change occurred in 5 patients and progression in 2 patients. In 7 patients, response could not be assessed. Median survival for all of the 41 eligible patients was 26 months. Severe leucopenia and thrombocytopenia were common and necessitated dose reductions or delays in 60% of patients. From a clinical point of view, the most severe non-haematological toxicity was renal dysfunction, and one patient died of this
Cancer Research, 2011
Purpose : Molecular classification of breast cancer (BC) through immunohistochemistry classifies ... more Purpose : Molecular classification of breast cancer (BC) through immunohistochemistry classifies patients globally in 4 subtypes with similar features and prognosis. The present study was designed to compare features of BC subtypes in early versus locally advanced clinical stages. A secondary objective was compare molecular subtypes of the primary vs recurrences. Methods : The study included 1621 patients with non-metastatic invasive BC that were consecutively diagnosed at Hospital Universitario 12 de Octubre, Madrid, between 1997 and 2007. Luminal A was defined as ER+ and PR+, HER2−negative and Ki67 < 14%. Luminal B was defined as PR-negative, HER2−positive or ki67≥14%. HER2 was defined as ER and PR-negative, and HER2−positive.Triple negative (TN) were tumors with ER, PR and HER2 -negativity. Clinicopathological characteristics and outcomes were retrospectively reviewed. Variables were compared with the X2 test, and survival curves were evaluated with Kaplan-Meier method. Result...
Clinical and Translational Oncology, 2013
In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GE... more In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GE-ICO), the first ''Treatment Guidelines in Ovarian Cancer'' were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308-316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750-755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript. Keywords Ovarian cancer Á Treatment guidelines Á Chemotherapy Á Surgery Á First line Á Recurrent disease Methodology During one and a half-day meeting, several topics on the management of ovarian cancer (OC) were reviewed by a panel of experts from GEICO about different areas. Each
Oncology, 2010
Aim: To retrospectively assess the efficacy and safety of bevacizumab plus low-dose metronomic or... more Aim: To retrospectively assess the efficacy and safety of bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Patients and Methods: Patients with recurrent ovarian cancer and prior treatment with platinum- and taxane-based chemotherapy were included. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks plus oral cyclophosphamide 50 mg daily until disease progression or unacceptable toxicity. Response rates (RR) were determined according to RECIST criteria and by monitoring the CA 125 serum tumor marker according to Rustin’s criteria. The endpoints were progression-free survival (PFS), RR, overall survival (OS), and safety. Results: Thirty-eight patients were treated; 79% were platinum resistant and 21% were platinum sensitive. The median number of previous treatments was 4 (range 1–8). Seventy-nine percent of patients had received more than 2 previous lines of treatment. Eighty-one percent of pat...
Journal of Clinical Oncology
16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and... more 16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and on disease-free survival (DFS) in patients with advanced cervical cancer receiving concurrent chemo-radiotherapy. Methods: One hundred thirty six patients with advanced cervical cancer (stage: 12 IB2-IIA, 34 IIB, 71 IIIB, 19 IVA); histology: 86 epidermoid and 14 adenocarcinoma) were analyzed to detect c-erbB-2 level using an immunohistochemical method (Herceptest Dako). Cases c-erbB-2 (+3) were considered positive. All patients received pelvic radiotherapy, brachitherapy and concurrent chemotherapy with two schedules: 48 patients with tegafur (800 mg/day via oral) and 88 with tegafur (same doses) plus five cycles of weekly cisplatin 40 mg/m2/week iv. Results: Of the 136 biopsies, 32 (23.5%) were c- erbB-2 positive. The disease free survival to 3 and 5 years of the patients were 61% and 58% for c-erb-B2 negative and 36% and 36% for c-erb- B2 positive (p=0.02), respectively.We divided our...
Clinical and Translational Oncology
An information under Table 2 was published incorrectly. The correct data should read as follows: ... more An information under Table 2 was published incorrectly. The correct data should read as follows: Visceral involvement No
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, Jan 24, 2017
This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estr... more This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.02...
Journal of Clinical Oncology
Journal of Clinical Oncology
Journal of Clinical Oncology
AIP Conference Proceedings, 2006
The impedance assessment to measure gastric emptying and in general gastric activity has been rep... more The impedance assessment to measure gastric emptying and in general gastric activity has been reported since 1985. The physiological interpretation of these measurements, is still under research. This technique usually uses a single frequency, and the conductivity parameter. The frequency domain and the Fourier analysis of the time domain behavior of the gastric impedance in different gastric conditions (fasting state,
Revista clínica española, Jan 15, 1979
British journal of cancer, Jan 6, 2006
To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin tar... more To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival w...
Seminars in oncology, 1995
From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung can... more From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for t...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 1994
From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution. Forty-three of t... more From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution. Forty-three of the pts were female (15.5%). Median age at diagnosis was 20 years (newborn-70). Histology was dysgerminoma (D) in 14 pts (including 2 anaplastic D), endodermal sinus tumor (EST) in 9 pts, immature teratoma in 10 pts and mixed tumors in 10 pts. Primary locations were as follows: ovary (O) 33 pts and extragonadal (EG) 10 pts (pineal in 4 cases, mediastinum in 3, sacrum in 2 and pharynx in 1). Stage: I in 20 (16 O, 4 EG), II in 7 (5 O, 2 EG), III in 12 (10 O, 2 EG) and IV in 4 (2 O, 2 EG). Serum AFP was elevated in 20/22 non-dysgerminoma pts, HCG in only 5 pts and LDH in 15/36 pts. Ovarian tumors: all but one pt (biopsy only) underwent surgery: unilateral oophorectomy was performed in 15 pts and bilateral oophorectomy (+/- hysterectomy, +/- others) in 17 pts. Fourteen pts were rendered disease-free, 8 pts had residual tumor (RT) < 2 cm and 11 RT > 2 cm. Chemotherapy (PVB or BEP) was gi...
The Lancet Oncology, 2011
Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and over... more Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive fi rst interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48•4 months (IQR 42•0-56•5) and assess the eff ect of the extensive crossover to trastuzumab. Our analysis was by intention-totreat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a signifi cant benefi t in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78•6%) compared with the observation group (4-year disease-free survival 72•2%; hazard ratio [HR] 0•76; 95% CI 0•66-0•87; p<0•0001). Intention-to-treat analysis of overall survival showed no signifi cant diff erence in the risk of death (4-year overall survival 89•3% vs 87•7%, respectively; HR 0•85; 95% CI 0•70-1•04; p=0•11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22•8 months (range 4•5-52•7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer diseasefree survival events than patients remaining in the observation group (adjusted HR 0•68; 95% CI 0•51-0•90; p=0•0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot fl ush, headache, and diarrhoea. Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with signifi cant clinical benefi t at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.
International Journal of Gynecological Cancer, 2010
To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relap... more To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relapse in patients with advanced cervical cancer (CC) receiving concurrent chemoradiotherapy treatment. A total of 136 patients with advanced CC (FIGO stage: IB2-IIA [12]; IIB [34]; IIIB [71]; IVA [19]; including both epidermoid [86] and adenocarcinoma [14]) were analyzed to determine c-erb-B2 levels by immunohistochemistry (c-erb-B2 antibody; Dako, Glostrup, Denmark). Only c-erb-B2+++ biopsies were considered positive. All patients received pelvic radiotherapy, brachytherapy, and concurrent chemotherapy with 2 different regimens: 48 patients were treated with tegafur (800 mg/d orally) and 88 with tegafur (same doses) plus 5 cycles of weekly cisplatin 40 mg/m/wk intravenously. A total of 32 (23.5%) biopsies were considered c-erb-B2-positive. Three-year and 5-year DFS were 61% and 58% for c-erb-B2-negative patients and 36% and 36% for c-erB2-positive patients, respectively (P = 0.02). Patients were stratified in 4 groups according to their c-erb-B2 status and whether they received cisplatin. The group of patients with c-erb-B2 overexpression that did not receive platinum treatment had a higher rate of pelvic relapse (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), associated with a decreased DFS (P = 0.0014). c-erb-B2 overexpression may imply a poor prognosis for patients with advanced CC. Treatment with cisplatin-based radiochemotherapy improved outcome in these patients.
European Journal of Cancer, 2003
Carcinosarcomas of the female genital tract are highly malignant tumours composed of carcinomatou... more Carcinosarcomas of the female genital tract are highly malignant tumours composed of carcinomatous and sarcomatous elements. In the past, these tumours were frequently treated as sarcomas. However, a number of arguments, including the sensitivity of these tumours to platinum-based chemotherapy, suggest that these tumours behave more like poorly differentiated carcinomas. The European Organization for Research and Treatment of Cancer (EORTC) Gynaecological Cancer Group therefore decided to perform a prospective phase II study in patients with advanced or metastatic carcinosarcoma with an approach such as that used in gynaecological carcinomas. Eligible patients could have primary or recurrent disease, but prior radiotherapy or chemotherapy was not allowed. The treatment plan recommended upfront debulking, followed by chemotherapy with cisplatin, ifosfamide and doxorubicin. Patients who could be debulked to non-measurable disease remained eligible for the study, but the response assessment was restricted to patients who had measurable disease before the start of chemotherapy. A total of 48 patients (39 primary disease, 9 recurrent disease) were registered, 41 of them being eligible. In 9 patients, all macroscopic lesions could be removed, 32 patients were left with residual disease and were assessable for response. The overall response rate was 56%: a complete response (CR) was observed in 11 (34%) patients and partial response (PR) in 7 (22%) patients. No change occurred in 5 patients and progression in 2 patients. In 7 patients, response could not be assessed. Median survival for all of the 41 eligible patients was 26 months. Severe leucopenia and thrombocytopenia were common and necessitated dose reductions or delays in 60% of patients. From a clinical point of view, the most severe non-haematological toxicity was renal dysfunction, and one patient died of this