Dimosthenis Chrysikos

Molecularly targeted therapies in cervical cancer. A systematic review

Cervical cancer represents the third most common cause of female cancer mortality. Even with the best currently available treatment, a significant proportion of patients will experience recurrence and eventually die. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis, targeting epidermal growth factor receptor, cell cycle, histone deacetylases, cyclooxygenase-2 (COX-2), or mammalian target of rapamycin (mTOR). This is the first systematic review of the literature to synthesize all available data emerging from trials and evaluate the efficacy and safety of molecularly targeted drugs in cervical cancer. However, it should be stressed that relatively fewer molecularly targeted agents have been tested in cervical cancer in comparison with other cancer types; of note, no related phase 3 trials have been published and consequently no agent has been approved for use in clinical practice. Nevertheless, the promising results of bevacizumab in therapeutic trials for cervical cancer have shown that targeting the VEGF pathway is an attractive therapeutic strategy. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the cervix, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for cervical cancer.

Platinum derivatives during pregnancy in cervical cancer: a systematic review and meta-analysis.

OBJECTIVE: Cervical cancer is the most common solid carcinoma diagnosed during pregnancy; obviously, pregnancy adds complexity to treatment recommendations. We synthesized all available data and evaluated the efficacy and safety of the administration of platinum derivatives during pregnancy in cervical cancer. DATA SOURCES: Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov databases for the period up to September 7, 2012; the algorithm comprised a predefined combination of the terms “cervical,” “cancer,” “cisplatin,” carboplatin,” and “pregnancy.” METHODS OF STUDY SELECTION: Two investigators, working independently, searched the literature and extracted data from all studies that examined the efficacy and safety of platinum derivatives administered during pregnancy in cervical cancer. All cases in which therapeutic abortion was scheduled were excluded. Moreover, quantitative synthesis of the published articles was performed. TABULATION, INTEGRATION, AND RESULTS: Overall, 24 studies (48 pregnancies, 48 newborns [one twin pregnancy and one miscarriage]) were eligible. In relation to cisplatin, 47 pregnancies were identified, whereas regarding carboplatin administration, only one pregnancy was retrieved. Cisplatin was administered either as monotherapy or combined with bleomycin, 5-fluorouracil, paclitaxel, vincristine, and bleomycin, whereas carboplatin was given in combination with paclitaxel. In most cases (67.4%), a completely healthy neonate was born; all children were healthy with a median follow-up of 12.5 months. The mean delivery weight of newborns was 2,213 g. Complete and partial response was achieved in 10% and 63.4% of patients with cervical cancer, respectively, whereas stabilization and progression of the disease occurred in 23.3% and 3.3% of women in the case group. In the majority of women in the case group, chemotherapy was well tolerated. The median progression-free survival was 48.5 months. CONCLUSION: Cisplatin may play a significant role in the management of patients with cervical cancer during the second and third trimesters.

mTOR inhibitors in breast cancer: A systematic review

PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt pathway is heavily deregulated in breast cancer, the application of mTOR inhibitors in breast cancer patients seems warranted. This is the first systematic review according to PRISMA guidelines to synthesize all available data of mTOR inhibitors in all subcategories of breast cancer. The search strategy retrieved 16 studies evaluating everolimus (1492 patients), seven studies examining temsirolimus (1245 patients), one study evaluating sirolimus (400 patients) and two studies evaluating MKC-1 (60 patients). The Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study has marked a turning point in the evaluation of everolimus in the treatment of estrogen receptor positive breast cancer. Given the positive results, everolimus has entered NCCN 2012 guidelines, and its approval of its combination with exemestane by FDA and EMA is imminent. In addition, the promising antitumor activity and long-term disease control further suggest that mTOR inhibition with everolimus may provide an avenue for achieving long-lasting benefit from trastuzumab-based therapy in HER2-positive patients. Regarding temsirolimus, it seems that the agent may play, in the future, a role in the treatment of metastatic breast cancer; importantly, however, there is an unmet need to find its optimal target subpopulation.

Taxanes for breast cancer during pregnancy: a systematic review.

Landmark studies have established taxanes in the treatment of patients with breast cancer; however, recommendations regarding their administration during pregnancy are controversial. The present systematic review aims to synthesize all available data that stem exclusively from breast cancer case series to evaluate the efficacy and safety of taxanes during pregnancy. Overall, 16 studies (50 pregnancies) were eligible for the systematic review according to prisma guidelines. The mean age of patients with breast cancer at pregnancy was 34.6 years. The gestational age (GA) at chemotherapy administration varied from 12 to 36 weeks. The mean GA at delivery was 35.9 weeks. The mean weight of babies at delivery was 2380 g. In 76.7% of cases, a completely healthy neonate was born; in the remaining cases, a neonate who was dystrophic and premature, one with mild hydrocephalus, one with signs of bacterial sepsis, one with hyperbilirubinemia, one with apnea of prematurity, respiratory distress syndrome and gastroesophageal reflux, one with meconium-stained fluid, and another neonate with neutropenia and pyloric stenosis were reported. Ninety percent of children were completely healthy, with a median follow-up of 16 months; in the remaining cases, one child with recurrent otitis media, one with immunoglobulin A deficiency and mild constipation, and another child with delayed speech were reported. In conclusion, available data suggest that taxanes may potentially play a promising role in the optimal therapeutic strategy of patients with breast cancer diagnosed during pregnancy.

Fulvestrant and male breast cancer: a case series

women with HER2 positive MBC. Proc Am Soc Clin Oncol 2003; 22: (Abstr 294). 3. Fyfe GA, Mass R, Murphy M et al. Survival benefit of trastuzumab (Herceptin) and chemotherapy in older (age >60) patients. Proc Am Soc Clin Oncol 2001; 20: (Abstr 189). 4. Serrano C, Cortés J, De Mattos-Arruda L et al. Trastuzumab related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 2012; 23: 897–902.

Taxanes for Ovarian Cancer during Pregnancy: A Systematic Review

Objective: Ovarian cancer in pregnancy is uncommon; however, this diagnosis adds complexity to cancer treatment recommendations. This is the first systematic review to synthesize all available data and evaluate the efficacy and safety of taxanes during pregnancy in ovarian cancer. Methods: This systematic review was performed in accordance with PRISMA guidelines. All studies that examined the efficacy and safety of taxanes administered during pregnancy in ovarian cancer, regardless of sample size, were considered eligible. Results: Overall, 8 articles (11 pregnancies, 12 newborns) were retrieved for paclitaxel and 1 for docetaxel (1 pregnancy, 1 newborn). In 92.31% of cases a healthy child was born, with a median follow-up of 20 months. The mean weight of the babies at delivery was 2,381 g. One study providing follow-up until the 11th year of age reported a case of attention deficit disorder. In 6 out of 8 case reports providing survival data, the mother was alive and disease free at the end of follow-up (ranging from 9.75 to 45 months). Conclusion: Taxanes may play a significant role in the treatment of ovarian cancer patients during the 2nd and 3rd trimesters. Before that, the risk of abortion or congenital anomalies is increased.

Molecularly targeted therapies in metastatic pancreatic cancer: a systematic review.

Abstract Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable.

Pertuzumab in breast cancer: a systematic review.

Pertuzumab is a monoclonal antibody that represents the first among a new class of agents known as human epidermal growth factor receptor (HER) dimerization inhibitors. This is the first systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize all available data of pertuzumab in breast cancer. The search strategy retrieved 11 studies that evaluated pertuzumab. One study was conducted in the neoadjuvant setting (417 patients), whereas all the others dealt with patients with recurrent, metastatic, or refractory disease (1023 patients). Six studies were conducted in HER2(+) breast cancer population (1354 patients), whereas 5 studies (86 patients) were conducted in HER2(-) (or unknown HER2 status) disease. Pertuzumab is the most recent agent approved by the US Food and Drug Administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2(+) metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval has been based on data from a phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study. The antitumor activity with the significant reduction in the risk of progression or death, as reflected upon the increase of 6.1 months in median progression-free survival, indicates that pertuzumab may provide an avenue for achieving additional benefit for patients with HER2(+). Moreover, pertuzumab seems to have a putative role in the management of patients with HER2 who are resistant to trastuzumab. The promising role of pertuzumab in the neoadjuvant and adjuvant settings remains to be further investigated and established in the future.

Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report

IntroductionPrimary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushings syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature.Case presentationA 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushings syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease.ConclusionsEven though primary pigmented nodular adrenocortical disease is a rare cause of Cushings syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushings syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.

Breast ductal endoscopy: how many procedures qualify?

BackgroundBreast ductal endoscopy is a relatively new diagnostic method with ever growing importance in the work-up of patients with bloody nipple discharge. The ability to perform ductal endoscopy is very important and useful for breast fellows. Learning curve in breast ductal endoscopy remains a terra incognita, since no systematic studies have addressed this topic. The purpose of this study is to determine the point (number of procedures during training) beyond which ductal endoscopy is successfully performed.FindingsTen breast fellows received training in our Breast Unit. For the training process, an ex vivo model was adopted. Fellows were trained on 20 surgical specimens derived from modified radical mastectomy for breast cancer. The target of the education program was to acquire proficiency in performing ductoscopy. The achievement of four consecutively successful ductal endoscopies was determined as the point beyond which proficiency had been achieved. The number of procedures needed for the achievement of proficiency as defined above ranged between 9 and 17 procedures. The median value was 13 procedures; i.e. 50% of trainees had achieved proficiency at the 13th procedure or earlier.ConclusionThese pilot findings point to approximately 13 procedures as a point beyond which ductal endoscopy is successfully performed; studies on a larger number of fellows are nevertheless needed. Further research, focusing on the learning curves of different training models of ductal endoscopy, seems desirable.