Immunohistochemical analysis of tumour regression grade for rectal cancer after neoadjuvant chemoradiotherapy.

AIM: Tumour regression grade (TRG) as defined by Rödel et al. has been used as an independent prognostic factor for rectal carcinoma after preoperative treatment by chemoradiotherapy (CRT). Determination of TRG 2 and 3, semiquantitatively defined as more or less than 50% tumour regression, respectively, does not appear to correlate with prognosis. The purpose of this study was to find an immunohistochemical pattern to permit improved stratification of intermediate responders defined by disease free (DFS) and overall survival (OS). METHOD: Immunohistochemistry of EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), CD133 antibody, p53 antibody and Ki67 antibody was evaluated using tissue microarrays (TMA) on post-treatment surgical specimens from 88 patients. CD133 expression was confirmed in the whole section when available. RESULTS: At a median follow-up of 40 months, TRG was found to be an independent predictor of DFS (P = 0.05) and OS (P = 0.001) but no differences were found between TRG 2 and 3 in terms of DFS (P = 0.74) or OS (P = 0.41). The results of TMA showed an immunohistochemically poor prognostic profile for intermediate responders configured by negativity of CD133 expression. However, when examining CD133 expression in the whole section, there was an intermediate correlation with TMA and the prognostic significance was lost. CONCLUSION: The results did not confirm the value of immunohistochemistry in predicting the prognosis of patients with rectal cancer following neoadjuvant chemoradiotherapy. This questions the accuracy of TMA in detecting CD133 expression in this setting.

Irinotecan-cetuximab-bevacizumab as a salvage treatment in heavily pretreated metastatic colorectal cancer patients: a retrospective observational study.

BACKGROUND: The objective was to evaluate the efficacy of irinotecan-cetuximab-bevacizumab in combination as a salvage treatment for heavily pretreated metastatic colorectal cancer patients. METHODS: A total of 39 patients resistant to both oxaliplatin and irinotecan were included in this retrospective study. Treatment consisted of irinotecan 180/m(2) every 14 days, weekly cetuximab standard dose and bevacizumab 5 mg/kg every 14 days. RESULTS: Partial response was observed in 8 patients (20%), stable disease in 24 (61%) and progressive disease in 7 (18%). Overall response rate in KRAS wild type was 6/22 (27%) and in mutated KRAS it was 2/15 (13%). Median time to progression was 8 months (6.4-9.4) and median overall survival 12 months (10.1-13.8). Overall, grade 3-4 adverse events were observed in 24 patients (62%). CONCLUSIONS: This regimen is active and moderately well tolerated in heavily pretreated advanced colorectal patients. However, caution is advisable when interpreting these results, because they run against the findings of two large phase III trials.

Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer.

BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance

Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: The purpose of this study was to identify clinical and pathological parameters to improve prediction of disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemoradiotherapy for rectal cancer. METHODS: Between July 1995 and May 2007, 148 patients with primary rectal adenocarcinoma received neoadjuvant chemoradiotherapy followed by mesorectal excision. Preoperative treatment included various protocols, UFT and leucovorin (28%) and oxaliplatin-based chemotherapy (72%). Clinical and pathological variables were evaluated in relation to patient outcomes. RESULTS: Thirteen percent of patients achieved a complete pathologic response. No response or minimal response as defined by Dworak (Tumor Regression Grade 0/1) was observed in 30 patients (20%). At a median follow-up of 37 months, the 3-year DFS and OS were 64% and 83%, respectively. Pre-treatment serum carcinoembryonic antigen (CEA) level

Pancreatic glucagonoma presenting as a pulmonary mass.

Glucagonoma is an uncommon disease, a neuroendocrine tumour that develops from glucagon-producing pancreatic cells. They are usually slow-growing, but generally advanced at diagnosis, and metastatic disease is virtually incurable. Liver is the most common site of metastatic disease. We present the case of a 48-year-old man with a glucagonoma being diagnosed from a pulmonary mass. This case had no liver affection in the whole evolution of the disease, and showed a particularly aggressive course, with very little response to all therapies administered, and a survival from diagnosis of just 16 months.

UFT (tegafur-uracil) in rectal cancer.

BACKGROUND: Major achievements in the treatment of localised rectal cancer include the development of total mesorectal excision and the perioperative administration of radiotherapy in combination with continuous infusion (CI) 5-fluorouracil (5-FU). This multimodal approach has resulted in extended survival and lower local relapse rates, with the potential for sphincter-preserving procedures. However, CI 5-FU is inconvenient for patients and is costly. Oral fluoropyrimidines like UFT (tegafur-uracil) offer a number of advantages over 5-FU. METHODS: We undertook a review of published articles and abstracts relating to clinical studies of UFT in the treatment of locally advanced rectal cancer (LARC). Pre- and postoperative studies carried out in patients with newly diagnosed or recurrent disease were included. RESULTS: The combination of UFT and radiotherapy was effective and well tolerated in the preoperative setting, while adjuvant UFT improved survival and reduced distant relapse compared with surgery alone. The efficacy of UFT appears comparable with that of 5-FU and capecitabine and its side-effect profile is favourable. CONCLUSION: Clinical experience to date suggests that UFT is a valuable treatment option for the perioperative treatment of LARC. Further improvements in patient outcomes may result from the combination of UFT with targeted agents.

Employment in a cohort of breast cancer patients.

BACKGROUND: Breast cancer survivors can have problems in returning to work. However, the importance of work to cancer survivors has until recently received little attention. AIMS: To investigate employment- and work-related disability in a cohort of breast cancer patients to identify possible discrimination and other obstacles to remaining in work. METHODS: Questionnaire study of breast cancer patients employed at diagnosis and where diagnosis had been confirmed at least 6 months before the interview. Participants completed a questionnaire concerning cancer-related symptoms and work-related factors and clinical details were obtained from their medical records. RESULTS: The study included 96 consecutive patients with breast cancer aged between 18 and 65 years. In total, 80% of patients were unable to work after diagnosis, but 56% returned to work at the end of treatment. The sequelae of the disease or its treatment and the stage of disease were independently associated with the ability to work after the end of treatment. Only one patient did not tell his/her employers and coworkers about his/her disease. In total, 29% noticed changes in their relation with co-workers and managers, usually in the sense that they tried to be helpful. None reported job discrimination. CONCLUSION: Breast cancer survivors in this study encountered some problems in returning to work, mainly linked to the sequelae of their disease and its treatment rather than to discrimination by employers or colleagues.

An epidemiological study of the perception of asthenia by oncologists in cancer patients: POA study.

INTRODUCTION: Despite the high prevalence of asthenia in cancer patients, around 50-75%, and its impact on quality of life, it continues to be a difficult symptom to assess and manage. This study defines the extent of perception and diagnosis of asthenia associated with cancer among Spanish oncologists. METHODS: A descriptive, observational study conducted in Spain based on a five-part structured questionnaire available to participants through a private website. RESULTS: The 100 oncologists surveyed, most in the public healthcare setting, diagnose asthenia in 58-70% of cases. They consider old age (56.5%) and advanced-stage disease (94.2%) as factors associated with the occurrence of asthenia, which is also common in, particularly, tumours, such as pancreatic cancer (30.4%), and some therapies, notably chemotherapy alone (67%) or combined with radiotherapy (96%). Despite its adequate detection, physicians rarely ask their patients about asthenia, use instruments for its evaluation or assess its impact on quality of life. Likewise, only 40% of all patients are treated, although therapeutic intervention, a multidisciplinary approach combining drug and non-drug treatments and managing a variety of causative factors, can be considered adequate. Finally, 91.5% of those surveyed do not have action guidelines for asthenia in their hospitals. CONCLUSIONS: Even when asthenia is widely diagnosed in cancer patients in Spain, there is a laxity in its assessment and treatment. Increased awareness among healthcare professionals of its impact and relevance is therefore required, as well as adequate protocols for its systematic detection and management within the routine assessment and treatment of cancer patients.

Cardiac toxicity: old and new issues in anti-cancer drugs.

Although rare, cardiotoxicity is a significant complication of cancer treatment. The incidence and severity of cardiovascular side effects are dependent on the type of drugs used, dose and schedule employed, and age of patients, as well as the presence of coexisting cardiac diseases and previous mediastinal irradiation. Classically, anthracyclines are among one of the most active agents in oncology, but their use is often hampered by their cumulative dose-limiting cardiotoxicity. In the past decade, combination therapy with new drugs such as taxanes or anti- EGFR, and Her-2 therapy as a single agent have also resulted in unexpected cardiotoxicity. Cardiac damage can be secondary to an alteration of cardiac rhythm, changes in blood pressure and ischaemia, and can also alter the ability of the heart to contract and/or relax. The clinical spectrum of these toxicities can range from subclinical abnormalities to being catastrophic, life-threatening and sometimes fatal. Knowledge of this toxicity can aid clinicians to choose the optimal and least toxic regimen suitable for an individual patient. In this work we present an exhaustive review of the cardiovascular side effects associated to new anticancer drugs, from new formulations of anthracyclines to tyrosine kinase inhibitors and monoclonal antibodies.

EGFR and colon cancer: a clinical view.

Signalling pathways that emerge from EGFR activation are critical in colon cancer (CC) biology. Its targeting with specific drugs has opened a new window in the treatment of this disease. In this regard, monoclonal antibodies (mAb) have evidenced a high degree of efficiency opposed to the uselessness of tyrosine-kinase inhibitors. Cetuximab is the mAb that has evidenced most activity in CC. After its initial approval as an irinotecan-resistance reversal agent, cetuximab has demonstrated its efficiency from the first line to heavily pretreated patients. In the first line, its addition may increase response rate to chemotherapy, improving liver metastases resection rate. Another promising approach has been suggested from combination schedules with bevacizumab. Panitumumab has been recently approved for CC. Although there is limited clinical experience, the latest data have confirmed its activity in heavily pretreated patients resulting in a clinical benefit vs. best support care. In spite of the clinical benefits, adverse events and the high sanitary cost derived from these drugs force the selection of patients with the highest probability of benefit. At the moment, when EGFR expression evidenced by immunohistochemistry has no value, skin toxicity and, fundamentally, K-Ras mutations may hint at critical information for confirmatory prospective studies.

Study of the prevalence of tumour-related asthenia in Spanish cancer patients.

INTRODUCTION: Asthenia is the most prevalent symptom in oncological patients but it is underestimated by the majority of healthcare professionals. The aim of the present study is to estimate the prevalence of tumour-related asthenia in the Spanish population, while defining the associated factors. METHODS: An epidemiological, multicentre, cross-sectional study was conducted in oncology services from Spain, including 712 cancer patients (58.4+/-13.5 years). RESULTS: 42.5% patients showed asthenia. This prevalence appeared to be tumour-related (p<0.05) and increased among patients with a more advanced stage of disease or with a worsening of performance status (p<0.001). The prevalence of asthenia increased in the presence of the following factors: chemotherapy (in the past: 52.1% vs. 31.0%; at the time of the study: 46.1% vs. 38.2%), symptomatic treatment (in the past: 60.4% vs. 39.8%; at the time of the study: 61.3% vs. 38.6%), present interferon treatment (100%), anaemia (59.7% vs. 31.3%), dehydration/waterelectrolyte imbalance (58.3% vs. 41.6%), respiratory failure (61.4% vs. 39.7%), liver disease (59.5% vs. 41.3%), malnutrition (76.1% vs. 38.7%), pain (57.7% vs. 27.0%), anxiety (56.1% vs. 38.6%), depression (57.9% vs. 40.0%) and sleep disturbances (51.1% vs. 39.4%). A multivariate logistic regression showed that a model including performance status, patient circumstance, chemotherapy, anaemia, pain and anxiety correctly diagnosed asthenia in 70.9% of cases. CONCLUSIONS: The physiopathology of tumour-related asthenia remains relatively unknown, despite its high prevalence and considerable quality of life impact. Determining factors related to asthenia in clinical practice can favour the use of concrete treatments and improve the conditions of cancer patients.

MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) that, in turn, mediates induction of apoptosis. In analysing surgical tissue samples of NSCLC, we found that expression of MKP1/CL100, a negative regulator of JNK, showed a strong nuclear staining for tumor cells, whereas, in normal bronchial epithelia, MKP1 was localized in the cytoplasm as well as in nuclei. In the NSCLC-derived cell lines H-460 and H-23, we found that MKP1 was constitutively expressed. Expressing a small-interfering RNA (siRNA) vector for MKP1 in H-460 cells resulted in a more efficient activation by cisplatin of JNK and p38 than in the parental cells, and this correlated with a 10-fold increase in sensitivity to cisplatin. A similar response was also observed in H-460 and H-23 cells when treated with the MKP1 expression inhibitor RO-31-8220. Moreover, expression of a siRNA-MKP2, an MKP1-related phosphatase, had no effect on H-460 cell viability response to cisplatin. Tumors induced by H-460 cells expressing MKP1 siRNA grew slower in nu(-)/nu(-) mice and showed more susceptibility to cisplatin than parental cells, and resulted in an impaired growth of the tumor in mice. On the other hand, overexpression of MKP1 in the H-1299 NSCLC-derived cell line resulted in further resistance to cisplatin. Overall, the results showed that inhibition of MKP1 expression contributes to a slow down in cell growth in mice and an increase of cisplatin-induced cell death in NSCLC. As such, MKP1 can be an attractive target in sensitizing cells to cisplatin to increase the effectiveness of the drug in treating NSCLC.

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) expression is downregulated in poorly differentiated breast invasive ductal carcinoma.

Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) is the only known enzyme able to reduce lipid peroxides bound to cell membranes. Moreover it has been involved in apoptosis and can influence intracellular signaling. To investigate the possible relationship between PHGPx and human cancer we have quantified PHGPx expression levels by real-time quantitative PCR and immunohistochemistry in tissue samples of human breast invasive ductal carcinoma from 34 patients compared with their own controls of benign breast tissue. PHGPx expression levels were compared with the clinical and pathological data of these patients. The results showed that PHGPx expression levels are downregulated in poorly differentiated (grade 3) breast invasive ductal carcinoma (P = 0.0043). PHGPx expression levels decreased gradually with tumor grade from grade 1 to grade 3. We also found a downregulation of PHGPx in cases that showed p53 accumulation compared with cases without p53 immunostaining (P = 0.0011). PHGPx was also downregulated in cases without progesterone receptors (PR) immunostaining compared with cases with PR immunostaining (P = 0.0165). Grade 3, p53 immunostaining and absence of PR immunostaining are poor prognostic factors. These results suggest that PHGPx downregulation could be related with a poorer prognosis in breast invasive ductal carcinoma.

Molecular markers in colorectal cancer: genetic bases for a customised treatment.

Colorectal cancer (CRC) is the second leading cause of cancer death in Western countries. CRC treatment is based on the employment of three chemotherapeutic drugs, including 5-fluorouracil, oxaliplatin and irinotecan, and the use of recently incorporated targeted agents directed to vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). The approval of these biologicals and of others to come holds great promise for the improvement of patient outcome. The molecular bases for this lethal disease have been extensively investigated, laying the foundations for a rational and customised treatment approach, expanding the therapeutic index of current drugs and easing the incorporation of new molecules. Individual markers have been mainly investigated based on drug targets and metabolism. Also, the increasing availability of highthroughput technologies has prompted the opportunity for blind studies capable of screening new markers and of identifying the specific oncogenic pathways responsible for drug resistance in a given patient. An updated review of the field is presented in this article.

Oxycodone: a pharmacological and clinical review.

Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone--which is also a very potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40- or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm) is also available in capsules and oral solution. Side effects are those common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus and dizziness are less common. The intensity of these side effects tends to decrease over the course of time. Oxycodone causes somewhat less nausea, hallucinations and pruritus than morphine.

New screening method for lung cancer by detecting volatile organic compounds in breath.

Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screening process and this limits its detection to the late stages, with consequently high mortality rates. Volatile organic compounds (VOC) are chemical compounds (mainly the products of cell catabolism) found as gases in the human breath. Different methods have been developed to analyse VOCs and to compare them in healthy subjects and lung cancer patients. In this review, we summarise the different techniques used to analyse VOC. Many reports have been published with promising results similar to those achieved with accepted screening methods such as mammography. These methods show good perspectives on lung cancer screening.

Brain metastases as the first sign of colon cancer.

Cerebral metastases from colorectal cancer occur in 8% of cases. Diagnosis is usually made when primary disease and widespread metastases are already known. However, the detection of brain metastases as the first sign of colorectal carcinoma without any liver and/or lung involvement is extremely rare. Central nervous system metastases are more commonly seen in rectal cancer and often occur concurrently with lung metastasis. We report a case of a patient with brain metastases as the first clinical manifestation of an adenocarcinoma of caecum without any other organ involvement.

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer.

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m2) followed by mitomycin C (8 mg/m2) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3-4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6-21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. CONCLUSIONS: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.

Control of oncologic pain in relief of suffering. Our experience.

BACKGROUND: Pain and suffering are not synonymous terms. The concept of suffering is wider than just physical pain. People can suffer for multiple causes, pain among them, but it is not the only reason since <>. If our main objective is the achievement of the well-being and the relief of pain, it will be necessary, according to Lazarus, Folkman, Chapman, Gravin, Bayés and Labrador, to reduce or eliminate the physical (cancer, pain and so on) and psychosocial harm (loneliness, culpability, etc.) perceived like a threat and to increase the perception of control about this situation. AIMS: The main objectives of our work were: First: to evaluate the efficacy of a tool that allows the identification of the symptoms perceived by the patient as a threat in order to reduce or suppress them and empower their resources at the same time; and secondly to evaluate the incidence of pain in the suffering. MATERIALS AND METHODS: Our tool includes the following groups of variables: subjective perception of the time course, emotional aspects, concerns and confrontation strategies, perception of adaptation and sense of life, perceived support and pain. This tool has been tested in 73 oncologic patients, 31 men and 42 women, mean aged 55, 41 (SD = 14, 54) visited at the Medical Oncology Service of La Paz Hospital. RESULTS: Mainly, people who refers great suffering are those with more pain (p < 0.05); while patients with less suffering and higher well-being are those that use strategies to face their situation (p < 0.05). Our tool reduces perceived threats and that reflects the need for a good control of pain and at the same time to empower the resources to relieve the suffering as much as possible. CONCLUSION: The referred tool seems to be effective in order to easy the intervention to relieve the suffering.

Strategies to accomplish targeted expression of transgenes in ovarian cancer for molecular therapeutic applications.

PURPOSE: The purpose of the study was to determine the capability of the midkine (MK) and cycooxygenase-2 (cox-2) gene promoter regions to function as tumor-specific promoters for use in targeted gene therapy of ovarian cancer. EXPERIMENTAL DESIGN: Established and primary ovarian cancer and mesothelial cells were transduced by adenoviral vectors containing a reporter or thymidine kinase gene expressed under the control of the MK, cox-2, or cytomegalovirus (CMV) promoters. SCID or C57BL/6 mice were injected i.p. with these same vectors. In vitro reporter gene expression and cellular cytotoxicity was determined using luciferase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. Acute toxicity in vivo was assessed by histological evaluation of harvested tissues. RESULTS: Consistent activation of the MK and cox-2 promoters was noted in all of the ovarian cancer cell lines in addition to primary ovarian cancer cells. In contrast, reduced reporter activity was reported in mesothelial cells transduced with adenoviruses containing the test promoters, which was especially apparent for the cox-2 promoter. Additionally, the cox-2 promoter exhibited significantly lower reporter gene levels in liver and peritoneum than the control promoter in in vivo experiments. Tumor-cell killing induced by Adcox-2 MTK was comparable to that observed with AdCMVTK. However, a clear differential toxicity pattern was observed in favor of animals treated with Adcox-2 MTK when compared with controls. CONCLUSIONS: These data clearly demonstrate that the transcriptional control afforded by the cox-2 promoter is tumor-specific and is able to mitigate associated toxicity in normal tissue while maintaining therapeutic efficacy in the context of an ovarian cancer molecular chemotherapeutic approach.