ABREAST: a prospective, real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and quality of life of patients with metastatic breast cancer.

PURPOSE: The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. PATIENTS AND METHODS: The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. RESULTS: Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6-33.7], the median PFS was 6.2 months (95% CI 5.2-7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients' baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively. CONCLUSIONS: This prospective study provides further evidence on quality of life, efficacy, and safety of nab-paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line.

Cutaneous toxicities of antineoplastic agents: data from a large cohort of Greek patients.

PURPOSE: Cutaneous toxicities from novel anticancer treatments are an emerging problem in dermato-oncology. However, the prevalence of those toxicities and necessity of skin consultations are currently unknown. The purpose of our study was to perform an epidemiologic analysis of cutaneous toxicities that were referred to our cutaneous toxicity clinic in Athens, Greece. METHODS: All patients examined at the oncodermatology department over a 42-month period were included. Gender, age, type of cancer, type of antineoplastic treatment, and type of toxicity were recorded and analyzed. RESULTS: Four hundred fifty-nine patients (182 males, 277 females) with mean age (SD) 60.6 years (13.05) were included in the analysis. Six hundred seventy-two cutaneous toxicities were recorded. Chemotherapy-induced toxicities were the most commonly recorded incidents, with taxanes being the most commonly involved agent. Immune-related adverse events (IRAEs) have steadily increased over the past 3 years. Treatment modifications due to skin toxicities were more common in patients treated with targeted agents and immune checkpoint inhibitors than in those treated with chemotherapy. The toxicities that led to the most treatment modifications were acneiform eruptions and perionychias. The most common IRAEs recorded were psoriasis in 11 patients, followed by pruritus, macular rash, and lichenoid-type eruptions. In addition, 4 interesting cases of IRAEs are discussed. CONCLUSION: Antineoplastic treatments can lead to a wide range of cutaneous toxicities. Our study underlines the need for a multidisciplinary approach in oncologic patients. The dermatologists' role is crucial in effectively managing those reactions and preventing antineoplastic drug dose adjustments or discontinuation of treatment.

Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03).

BACKGROUND: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. PATIENTS AND METHODS: One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events). RESULTS: The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). CONCLUSIONS: Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.

Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study.

BACKGROUND: The ubiquitin-proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients. METHODS: Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose-dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one-step quantitative RT-PCR for assessment of mRNA expression of UBE2C. RESULTS: High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05). CONCLUSIONS: High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts.

Maintenance chemotherapy or not in ovarian cancer stages IIIA, B, C, and IV after disease recurrence.

PURPOSE: Ovarian cancer may have a high percentage of residual disease after chemotherapy. It is questionable whether second or more lines of chemotherapy are needed in patients with slow-growing residual disease. In the present trial we compared the median survival of patients with residual or recurrent disease who received 1-2 lines of chemotherapy with those who received 3-9 lines. METHODS: Two hundred and five patients with advanced stage IIIA, B, C and IV ovarian cancer were divided into two groups based on the number of chemotherapy lines they received. All patients had prior first-line chemotherapy; the criteria for recruitment in the study were: a) residual or recurrent disease and b) failure to respond to first-line therapy. Group A included patients who received 1 or 2 lines of chemotherapy and group B, 3-9 lines. RESULTS: The median survival of group A was 76 months and of group B 53 months (p<0.001). Complete response (CR) was observed in 80 out of the 193 7lpar;41.45%) evaluable patients, partial response (PR) in 37 (19.17%), stable disease (SD) in 54 (27.987percnt;) and progressive disease (PD) in 22 (11.40%) patients. CONCLUSION: In ovarian cancer patients with advanced disease, multiple chemotherapy lines (3=9) offer no advantage over 1 or 2 lines, with respect to overall survival.

Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer.

Trastuzumab (T) is effective in metastatic breast cancer (MBC) with HER2 overexpression and/or amplification, but resistance to T develops in a significant number of HER2-positive patients. Understanding the mechanisms of resistance is critical to the care of these patients. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 256 patients with T-treated MBC. Clinical information was collected retrospectively from the patients' medical records. Central review of HER2 status by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC) revealed that of the 227 eligible patients only 139 (61%) were truly HER2-positive. PTEN, ER, PgR, and Ki67 were evaluated by IHC, while PTEN status was evaluated by FISH as well. PIK3CA mutations were identified with single nucleotide polymorphism (SNP) genotyping. Median time to progression (TTP) was 14.4 months for the HER2-positive and 10.3 for the HER2-negative patients (log-rank, P = 0.22). Survival from the initiation of T (survivalT) was 50.4 months for the HER2-positive and 35.3 for the HER2-negative subgroups (P = 0.006). Higher risk of progression was associated with HER2-positive status and the presence of PIK3CA mutations (P = 0.014). PTEN loss, as determined by IHC, was associated with lower survivalT in the whole population (P = 0.029) and in the HER2-positive population (P = 0.017). PIK3CA mutations and/or PTEN loss status were evaluated together as a single parameter, to estimate the impact of activation of the PI3K/AKT molecular pathway, and it was significantly associated with both decreased TTP (P = 0.003 in the total population, P = 0.004 in HER2-positive patients) and survival (survivalT, P = 0.011 in total, P = 0.006 in HER2-positive). In this trastuzumab-treated breast cancer population, PIK3CA activating mutations were associated with shorter TTP and PTEN loss with decreased survival. The activation of the PI3K/AKT pathway from either defect was associated with both TTP and survival, indicating the adverse effect of this pathway's status on trastuzumab efficacy.

Randomized multicenter phase II trial of cisplatin and ifosfamide with or without paclitaxel in recurrent or metastatic carcinoma of the uterine cervix: a Hellenic Cooperative Oncology Group (HeCOG) study.

BACKGROUND: We undertook a randomized phase II trial to test whether the addition of paclitaxel (Taxol) to the cisplatin and ifosfamide (IP) combination could improve objective response (OR) rate, progression-free survival (PFS) and overall survival (OS) in patients with recurrent or metastatic cancer of the uterine cervix. PATIENTS AND METHODS: One hundred and fifty-three patients were randomly allocated to receive either the IP regimen (ifosfamide 1.5 g/m(2), daily, on days 1-3 and cisplatin 70 mg/m(2) on day 2) or the same combination with the addition of paclitaxel 175 mg/m(2) on day 1 [ifosfamide, paclitaxel and cisplatinum (ITP) regimen]. Cycles were administered every 4 weeks on an outpatient basis. RESULTS: A modest increase in neurotoxicity was observed with the triplet combination. OR rate was significantly higher in the ITP group (59% versus 33%, P = 0.002). Median PFS was 7.9 and 6.3 months for patients in the ITP and IP arms, respectively (P = 0.023). Median OS was 15.4 months and 13.2 months in the ITP and IP arms, respectively (P = 0.048). In multivariate analysis, the triplet yielded a hazard ratio of 0.70 for relapse or progression (P = 0.046) and 0.75 for death (P = 0.124) compared with the doublet. CONCLUSION: The ITP combination merits further investigation in randomized phase III studies.

A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: a Hellenic Cooperative Oncology Group study.

BACKGROUND: Effective anthracycline-free combinations need to be evaluated in metastatic breast cancer (MBC), due to the increased number of patients treated with anthracycline-based adjuvant chemotherapy. PATIENTS AND METHODS: Patients with MBC were randomized to paclitaxel and carboplatin (PCb) every 3 weeks or docetaxel and gemcitabine (GDoc) every 3 weeks or weekly paclitaxel (Pw). Trastuzumab was given to patients with HER-2 over-expressing tumors. The primary endpoint of the study was survival. Quality of life (QoL) and cost were assessed. RESULTS: Totally, 416 eligible patients entered the study. Median survival times were 29.9 months for PCb, 26.9 for GDoc and 41.0 for Pw (P = 0.037). According to multivariate analysis, adjuvant chemotherapy, >1 metastatic sites, lack of maintenance hormonal therapy, and worse performance status (PS) were significant adverse prognostic factors for survival, while Pw when compared to GDoc improved survival (P = 0.03), as well as when compared to PCb in the subgroup of patients with PS = 1 (P = 0.01, treatment by PS interaction P = 0.03). No significant differences in terms of time to progression were found. Severe myelotoxicity and mucositis were more frequent with GDoc, while severe neuropathy with PCb and Pw. QoL changes did not differ significantly between treatment groups, while cost analysis favored Pw. CONCLUSIONS: Pw appears to be the most preferable choice among the 3 anthracycline-free taxanes-based regimens tested in the present study.

Primary fallopian tube carcinoma: results of a retrospective analysis of 64 patients.

OBJECTIVE: The objective of this retrospective study was to determine the clinical outcomes of patients with primary fallopian tube carcinoma (PFTC) treated with paclitaxel and platinum analogue-based combination chemotherapy following primary cytoreductive surgery. METHODS: Sixty-four patients with the diagnosis of PFTC were identified through the gynecology service database and the tumor registry of 4 different institutions. The majority of patients (48/64, 75%) were treated with carboplatin AUC (area under curve) 6 and paclitaxel 175 mg/m(2) as a 3 h infusion. RESULTS: Among 28 patients with measurable disease, we observed 19 (68%) complete clinical and 7 (25%) partial responses for an overall response rate of 93%. After a median follow-up of 40 months (3+-134+ months), the 5-year survival rate of the entire population was 70% (median overall survival [mOS] not reached) and the median time to tumor progression (mTTP) was 81 months (95% CI: 53-109). Stage and residual disease were of prognostic significance. The mTTP was not reached in patients with stage I/II and was 38 months for patients with stage III/IV (p=0.004). The mOS for patients with stage I/II was not reached, whereas it was 62 months for those with stage III/IV (p=0.057). The mTTP was 86 and 23 months for patients with residual disease <2 cm and >2 cm, respectively (p<0.001). The mOS was not reached for patients with residual disease <2 cm, while it was 36 months for residual disease >2 cm (p<0.001). CONCLUSION: Optimally cytoreduced patients with PFTC treated with platinum and paclitaxel-based chemotherapy regimen have an excellent possibility of survival.

Effects of epoetin-alpha on quality of life of cancer patients with solid tumors receiving chemotherapy.

BACKGROUND: Erythropoietin corrects and prevents anemia and decreases the need for red blood cell (RBC) transfusions; its impact on quality of life (QOL) of cancer patients receiving chemotherapy is not clear. PATIENTS AND METHODS: 399 patients with solid tumors and Hb level of < or = 12 g/dl receiving chemotherapy were randomized to receive or not 10,000 IU epoetin-alpha thrice weekly. QOL was measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale and various subscales at baseline, at two months and at the end of the study. RESULTS: Changes in the average QOL scores were similar in the two groups. The improvement in Hb levels was significantly higher for the epoetin-alpha group, with a decrease in transfusion requirements compared to the control group. CONCLUSION: Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales, despite improving Hb levels and reducing transfusion requirements.

Analysis of 7 immunohistochemical markers in male germ cell tumors demonstrates the prognostic significance of p53 and MIB-1.

BACKGROUND: Various prognostic factors have been investigated in order to predict the minority of male germ cell tumor (GCT) patients who will develop resistant disease. However, no prognostic system has been proven accurate. MATERIALS AND METHODS: Paraffin-embedded tissue specimens, obtained from primary lesions during the initial diagnosis of 83 advanced chemotherapy-treated GCT male patients, were stained for 7 immunohistochemical markers: p53, bax, bcl-2, MIB-1, topoisomerase IIa, c-kit and COX-2. The percentage of positive cells for each marker was measured for each patient. Cox regression was used for the prognostic factor analysis. RESULTS: All patients were followed for a median of 4 years. Nineteen patients had seminoma and 64 non-seminomatous GCT. In univariate analysis, only p53 (hazard ratio (HR) = 4.01, 95% confidence interval (CI) = 1.25-12.84, p = 0.019) and MIB-1 (HR = 3.16, 95% CI = 1.06-9.45, p = 0.039) were found to be prognostic for disease-specific survival. The best prognostic cut-off values of p53 and MIB-1 were 10% and 30% respectively. In multivariate analysis, these two markers obtained independent significance only when considered in combination (HR = 6.63, 95% CI = 1.40-31.41, p = 0.017, for patients with one or both markers above their cut-off), while the International Germ Cell Consensus Cancer Group (IGCCCG) risk was the most significant (HR = 7.99, 95% CI = 1.96-32.52, p = 0.004, for the high-risk group). However, the expression of these markers seemed to be significantly correlated with known prognostic factors. Nevertheless, we identified 34 patients of low IGCCCG risk expressing both markers below their cut-off with excellent survival. CONCLUSION: Among 7 immunohistochemical markers, p53 and MIB-1 demonstrated prognostic significance. Their combination may contribute to improvement of the accuracy of the currently approved prognostic system (IGCCCG).

Epithelial ovarian cancer in Greece: a retrospective study of 1,791 patients by the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: The aim of this retrospective study was to present the epidemiological, pathological and clinical characteristics and treatment results of Greek women with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: From February 1976 to December 2006, 1,791 patients had been diagnosed, treated and followed up in the participating centers of the Hellenic Cooperative Oncology Group (HeCOG). Cox-regression analysis was carried out in order to identify possible prognostic factors. RESULTS: The median age at diagnosis was 60 years. Seventy-five percent had a performance status (PS) of 0-1, 58.5% had a serous carcinoma, 36% had poorly differentiated tumors and 57% had International Federation of Gynecology and Obstetrics (FIGO) stage III disease. Approximately half of the patients had been subjected to a total abdominal hysterectomy, bilateral oophorectomy and omentectomy, and 80% of them had undergone optimal debulking surgery. Among 1,462 patients with advanced disease, 96% had received platinum-based chemotherapy, while platinum plus paclitaxel had been administered to two-thirds of them. Among 609 patients with known data for response, 34% had achieved a complete objective response (CR) and 30% a partial response (PR), resulting in an overall response rate (RR) of 64%. Performance status, FIGO stage and residual disease (RD) after cytoreductive surgery were the strongest prognostic factors for time-to-tumor progression (TTP) and for overall survival (OS), while age was found to be significant only for OS. The median TTP was 107 months (95% confidence interval (CI), 92-121 months) for patients with stages I-II, 17 months (95% CI, 15-18 months) for those with stages III-IV 96 months (95% CI, 58-133 months) for patients without RD and 17 months (95% CI, 15-18 months) for those with RD. Median OS had not been reached for the patients with stages I-II, while it was 40 months (95% CI, 37-43 months) for those with stages III-IV, 141 months (95% CI, 103-179 months) for patients without RD and 42 months (95% CI, 39-45 months) for those with RD. CONCLUSION: There were no significant differences in patient characteristics or types of treatments administered in Greek women with EOC in comparison with those reported in the English literature.

Association between genetic polymorphisms in long non-coding RNAs and pancreatic cancer risk.

BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), deregulation of lncRNAs involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression. OBJECTIVE: The aim of our study was to investigate the contribution of two lncRNAs polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility. METHODS: A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a population-based case-control study of pancreatic cancer (111 pancreatic ductal adenocarcinoma cases (PDAC), 56 pancreatic neuroendocrine tumor (PNET), and 125 healthy controls). RESULTS: Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients. CONCLUSIONS: Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results.

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study.

The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT-PCR). The overall concordance between kRT-PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT-PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.

High-dose melphalan and autologous stem cell transplantation as consolidation treatment in patients with chemosensitive ovarian cancer: results of a single-institution randomized trial.

The role of high-dose chemotherapy (HDCT) in epithelial ovarian cancer (EOC) remains controversial. This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC (FIGO stages IIC-IV). Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were randomly assigned to receive or not high-dose melphalan. The primary objective was to compare time to disease progression (TTP). A total of 80 patients were enrolled onto the trial. Patients who were randomized to receive HDCT were initially treated with cyclophosphamide 4 g/m(2) for PBPC mobilization. HDCT consisted of melphalan 200 mg/m(2). Of the 37 patients who were allocated to HDCT, 11 (29.7%) did not receive melphalan either due to patient refusal (n=5) or due to failure of PBPC mobilization (n=6). In an intent-to-treat analysis, there were no significant differences between the two arms in TTP (P=0.059) as well as in overall survival (OS) (P=0.38).

Multicenter phase-II trial of irinotecan plus oxaliplatin [IROX regimen] in patients with poor-prognosis cancer of unknown primary: a hellenic cooperative oncology group study.

BACKGROUND: Cancer of unknown primary (CUP) lacks established therapy although it affects 3% of cancer patients. We evaluated the irinotecan-oxaliplatin combination (IROX regimen) in previously untreated patients with non-favorable subsets of unknown primary carcinomas. METHODS: This was a multicenter phase-II trial. Protocol treatment consisted of oxaliplatin 80 mg/m(2) followed by irinotecan 160 mg/m(2) administered every 3 weeks. The primary end points were response rate and toxicity, and secondary end points were time to progression and survival. RESULTS: Forty-seven patients with liver, bone or multiple visceral metastases entered into the trial and received a median 6 chemotherapy cycles (1-11). The regimen was very well tolerated with one febrile neutropenia case and six cases with diarrhea grade 3 (16%). In intent-to-treat analysis the tumor response rate was 13% (95% CI = 4.8-25.7%) and 12 patients (27%, 95%CI 13.9-40.4%) had at least 4 months' duration of disease stabilization. The median time to progression was 2.7 months and the median survival was 9.5 months, with 40% of patients alive at 1 year. CONCLUSIONS: The IROX regimen demonstrated similar efficacy and a favorable toxicity profile compared to other more toxic chemotherapy combinations in patients with poor-prognosis CUP.

Adult granulosa cell tumors of the ovary: a clinicopathological study of 34 patients by the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: Granulosa cell tumors (GCT) are rare malignant neoplasms of the ovaries with, usually, indolent biological behavior. PATIENTS AND METHODS: The epidemiological, clinical and pathological features of 34 patients with adult GCT, from the registry of the HeCOG, were analyzed retrospectively for their prognostic significance. RESULTS: The median age was 51 years with post- to premenopausal ratio=l.8 and median size of the tumor 10 cm. Forty-seven % had a low mitotic index (1-3 mitoses/10 high-power fields, HPFs) and 48% had International Federation of Obstetrics and Gynecology (FIGO) stage IA. After 34.5 months of median follow-up, the estimated 5-year and 10-year progression-free survival (PFS) was 78% and 65%, respectively, while both the 5- and 10-year overall survival (OS) was 89%. The stage and the presence of residual disease after surgery had prognostic significance for OS in the univariate analysis. Out of 19 patients whose disease was completely resected, the median disease-free survival (DFS) was 11 months. Only rupture of the tumor during surgery had prognostic significance for DFS in the univariate analysis. Seven out of 13 evaluable patients with unresectable disease responded to first-line chemotherapy (CT), 6 of them completely, while three patients responded to second-line chemotherapy. All the responders were retreated with platinum-based CT and one of them was platinum-insensitive. All the patients receiving second-line non-platinum CT developed progressive disease (PD). CONCLUSION: The only curative treatment of GCT is complete surgical resection of all visible disease, while platinum-based CT is the most effective first-line, as well as second-line treatment.

Weekly administration of topotecan-paclitaxel as second-line treatment in ovarian cancer.

PURPOSE: To investigate the weekly administration of topotecan combined with paclitaxel in pretreated advanced ovarian cancer patients; our objectives were to determine efficacy, toxicity and survival. METHODS: The chemotherapy agents, topotecan and paclitaxel were administered on a weekly basis for 3 consecutive weeks, every 28 days. The plan was to give three courses (each course included three once-weekly infusions). The dose of topotecan was 1.75 mg/m(2) and of paclitaxel 70 mg/m(2). RESULTS: From January 2004 until January 2006, 45 patients were enrolled in this multicenter trial; 44 patients were evaluable for response and toxicity. The median age was 60 years old (range 39-82 years) and performance status was 0-2. Thirty-nine patients were in stage III and 5 in stage IV. All patients had been pretreated with carboplatin or cisplatin in combination with paclitaxel. Complete and partial responses were seen in 39% of the patients, stable disease in 43% and progressive disease in 18%; median survival time was 9 months, range 2-24+ months, (95% CI: 7.9-10.2). There was a notable absence of grade 3 toxicity except for neutropenia in 11% of the patients. CONCLUSION: The combination of topotecan and paclitaxel administered on a weekly basis is a well-tolerated chemotherapy schedule. The response rate of 39% is quite high for patients with pretreated ovarian cancer.

Kit expression in male germ cell tumors.

OBJECTIVE: KIT functions as the receptor for stem cell factor (SCF) and this interaction is essential for regulation of proliferation and survival, particularly for germ cells since it regulates oogenesis, folliculogenesis and spermatogenesis. Up-regulation of KIT signalling has been associated with oncogenic transformation in cells expressing the molecule. Our objective was to investigate the expression of KIT in germ cell tumor patients and correlate it with the patients' clinical characteristics. PATIENTS AND METHODS: One hundred and seventy-three archival blocks of formalin fixed, paraffin-embedded tumor samples from histologically confirmed germ cell tumor (GCT) patients were included in the study. Immunohistochemical staining for KIT was performed and the percentage of positive cells was calculated by an independent pathologist. KIT expression was considered as positive if > 10% of tumor cells displayed membranous or cytoplasmic staining. RESULTS: Sixty-one patients with seminomatous (49 pure, 11 anaplastic, 1 spermocytic) and 112 with non-seminomatous GCTs (36 malignant teratoma undifferentiated (MTU), 15 malignant teratoma trophoblastic (MTT), 20 malignant teratoma intermediate (MTI), 35 malignant teratoma combined (MTC) and six others) were identified. Among pure seminoma patients, 38 (77.5%) revealed a positive staining for KIT, while only two out of eleven (18.2%) anaplastic seminoma patients were identified as positive. This difference was statistically significant (p < 0.001). Among 35 patients with an MTC, 48.6% had a positive KIT staining while only two of the remaining patients with a non-seminomatous GCT had a positive staining. Although KIT was strongly correlated with seminomatous histology (p < 0.001), it failed to correlate with stage (p = 0.19) or treatment response (p = 0.11) in these patients. Overall, four (one seminoma, three MTC) out of 22 chemoresistant patients showed a positive staining for KIT. CONCLUSION: KIT is expressed in the majority of seminomas and in seminomatous components of the combined tumors, but only in a minority of anaplastic seminomas and rarely in non-seminomatous GCTs. The recent development of tyrosine kinase inhibitors may offer a possibility of cure in chemoresistant patients overexpressing KIT.

A randomized trial to compare the efficacy and safety of antiemetic treatment with ondansetron and ondansetron zydis in patients with breast cancer treated with high-dose epirubicin.

OBJECTIVE: The objective of this study was to compare the efficacy of a disintegrating tablet of ondansetron (ODT) and the conventional tablet formulation of ondansetron (OT) in controlling nausea and vomiting in breast cancer patients. PATIENTS AND METHODS: A total of 134 breast cancer patients receiving high-dose epirubicin participated in a randomized trial comparing the antiemetic efficacy and safety of an 8 mg OT given twice daily to an 8 mg orally ODT given twice daily, both for 3 days. RESULTS: OT was significantly better in the complete control of emesis (72% versus 52%, p=0.020) and marginally better in the complete control of nausea (66% versus 48%, p=0.054) induced by high-dose epirubicin over days 1-3 compared to ODT. However, no differences were found in major control of emesis (0 to 2 emetic episodes, 76% versus 70%, p=0.28) over days 1-3. CONCLUSION: OT was significantly better in the complete control of emesis and marginally better in the complete control of nausea, but not in the major control of emesis and nausea induced by high-dose epirubicin compared to ODT. ODT may be an effective alternative to OT, particularly in patients who have difficulties in swallowing a conventional tablet.