Personalized Cancer Treatment for Ovarian Cancer

Ovarian cancer is the seventh most common cancer in women in the United States, accounting for 3% of all malignancies and 6% of deaths from cancer in women, and it almost represents one third of invasive malignancies of the female genital organs and approximately 90% are serous cystadenocarcinoma, ovarian cancer is the fifth most common cause of death from malignancy in women. Unfortunately more than two thirds of patients have advanced disease at diagnosis. By consequence ovarian cancer, it has the highest fatality-to-case ratio of all the gynecologic malignancies. The 5-year survival rate for stage III-IV is only 11-41% (Berek and Natarajan, 2007). When recur, the (OR) ranges from 47.2-61.7% by various combination chemotherapies: [carboplatinepidoxorubicin (Bolis et al., 2001), cyclophosphamidedoxorubicin-cisplatin (Cantu et al., 2002), carboplatinpaclitaxel (Parmar et al., 2003), and carboplatingemcitabine (Pfisterer et al., 2006)] for platinum sensitive diseases. Markedly lower OR of 6.1-25.7% was reported with single agent chemotherapies: [topotecan (ten Bokkel et al., 1997), pegylated liposomal doxorubicin (Gordon et al., 2001), weekly paclitaxel (Rosenberg et al., 2002), docetaxel (Berkenblit et al., 2004), gemcitabine (Mutch et al., 2007), and bevacizumab (Cannistra et al.. 2007)] for platinum resistant diseases (NCI, 2012).


Introduction
Ovarian cancer is the seventh most common cancer in women in the United States, accounting for 3% of all malignancies and 6% of deaths from cancer in women, and it almost represents one third of invasive malignancies of the female genital organs and approximately 90% are serous cystadenocarcinoma, ovarian cancer is the fifth most common cause of death from malignancy in women.Unfortunately more than two thirds of patients have advanced disease at diagnosis.By consequence ovarian cancer, it has the highest fatality-to-case ratio of all the gynecologic malignancies.The 5-year survival rate for stage III-IV is only 11-41% (Berek and Natarajan, 2007).

Materials and Methods
Patients were educated on the regimen which they were to receive and given consent forms to complete prior to starting each medication as witnessed during the medical record review from the Burzynski Clinic (BC), Houston, Texas, on March 14, 2012.This retrospective study was done by extracting data from BC's patient records in the RESEARCH ARTICLE

Bandit Chumworathayi
USA, and all patient's medical records were reviewed from March 14-21, 2012.
Our group of patients was graded according to the 2002 American Joint Committee on Cancer (AJCC) staging criteria; only patients with stage III or IV predominately epithelial ovarian cancer with variable histology were included.Patients were evaluated for tumor response after the completion of first follow up imaging which was either computed tomography (CT) or positive emission tomography (PET) or PET/CT.Patients were evaluated for measurable disease -the presence of at least one measurable lesion.The measurable disease was assumed to be neoplastic in nature as verified by prior pathology report and in line with recurrence of disease.
We analyzed 33 patients deemed evaluable and each patient was assigned one of the following categories: 1) complete response 2) partial response 3) stable disease 4) progressive disease 5) minor response 6) minor response based on PET scan.
Complete Response (CR): Disappearance of all target lesions sustained for at least four weeks.CR by PET: no metabolic activity seen on PET scan.
Partial Response (PR): More than a 50% decrease in the sum of the longest perpendicular diameters of target lesions, taking as reference the baseline sum perpendicular diameter.
Partial Response by PET: Reduction SUV uptake and no new hypermetabolic lesions.
Minor Response Based on CT: Minor response (MR) at least 25% reduction in tumor size base on sum of perpendicular diameter.
Additional criteria: Minor response based on PET scan was defined as a decrease of metabolic activity.
Stable Disease based on CT (SD): Neither sufficient shrinkage to qualify for MR nor sufficient increase to qualify for PD, taking as reference the smallest sum largest perpendicular diameter since the treatment started.
Stable Disease based on PET: relative stable SUV uptake and no new lesions on PET.
Progressive Disease (PD): At least a 25% increase in the sum of the perpendicular diameters, or the appearance of one or more new lesions.
Of note a negative PET at baseline, with a positive PET at follow-up is PD based on a new lesion.No PET at baseline and a positive PET at follow-up: If the positive PET at follow-up corresponds to a new site of disease on CT, this is PD.If the positive PET at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the basis of the anatomic images, this is not PD.
Treated patients underwent routine blood tests such as a comprehensive metabolic panel, complete blood count, urinalysis and tumor markers such as CA-125.Additional testing of serum included analysis of Vascular Endothelial Growth Factor (VEGF range 40-92 pg/ mL), Epidermal Growth Factor Receptor (EGFR range 67-87 ng/mL), Human Epidermal Growth Her2/Neu Extracellular Domain (HER2/Neu range 0-12 ng/mL), and c-kit mutation status in serum.
Since 2010 patients began to be tested with more extensive molecular profiling of the tumor tissue which was embedded in paraffin or present in unstained slides.Testing which was performed by Caris Life Sciences included mutational analysis, immunohistochemistry (IHC) to determine the level of protein expression, fluorescence in situ hybridization (FISH) to detect gene deletions, amplifications, translocations and fusions, and a microarray analysis which is able to measure the level of RNA expression in twenty four thousand genes.Afterwards the treatment plan was formulated with this information and searching through the literature for further support.

Results
All 33 patients were summarized and shown in Table 1.All responses were analyzed and shown in Table 2. Objective Response Rate (OR) was found to be 42.4%.
The response rates found in other groups of ovarian cancer with heavily pretreated by chemotherapies and radiotherapies were also surprising as these patients should not have response rates as close to 40%.(NCI, 2012) However, response rates from personalized-targeted therapy are as at least 42.42% could be yielded.(Table 2).
Strength of this study is that there has never been any report of this kind of treatment before in the medical literature, as it is the innovative approach in treating cancers by Dr Burzynski SR.The weakness of this study may be that it was a retrospective study in which the data might be incomplete, and filled with some biases.With more patients in the future, a better report of this kind of treatment may be accomplished.
In conclusion, the goal of this paper is to present the various changing diagnostic and therapeutic possibilities in treating metastatic ovarian cancer to prevent resistance, give an improved quality of life and in essence a better outcome for patients.The original histological diagnostic techniques are limited and it is evident that the diversity in these tumors is intertwined with genomic instability, over expression of oncogenes, loss of tumor suppressor genes, up regulated signaling pathways fueling growth factors, angiogenesis and other features of tenacity of resistant ovarian cancer.Ideally eliminating neoplastic cells and neoplastic stem cells can be theoretically done with the proper pharmaceuticals which are aimed at each cancers genetic signature.The gynecological community is coming to agreement that the standard surgical debulking and front line chemotherapy needs to have additional agents included to focus on this heterogeneity of ovarian cancer.As the era of personalized cancer care has arrived, we can be optimistic that future treatments will be more effective due to improved molecular analysis and new therapeutics.