Physician-patient communication of costs and financial burden of cancer and its treatment: a systematic review of clinical guidelines.

BACKGROUND: Optimising the care of individuals with cancer without imposing significant financial burden related to their anticancer treatment is becoming increasingly difficult. The American Society of Clinical Oncology (ASCO) has recommended clinicians discuss costs of cancer care with patients to enhance shared decision-making. We sought information to guide oncologists' discussions with patients about these costs. METHODS: We searched Medline, EMBASE and clinical practice guideline databases from January 2009 to 1 June 2019 for recommendations about discussing the costs of care and financial burden. Guideline quality was assessed with the AGREE-II instrument. RESULTS: Twenty-seven guidelines met our eligibility criteria, including 16 from ASCO (59%). 21 of 27 (78%) guidelines included recommendations about discussion or consideration of treatment costs when prescribing, with information about actual costs in four (15%). Recognition of the risk of financial burden or financial toxicity was described in 81% (22/27) of guidelines. However, only nine guidelines (33%) included information about managing the financial burden. CONCLUSIONS: Current clinical practice guidelines have little information to guide physician-patient discussions about costs of anticancer treatment and management of financial burden. This limits patients' ability to control costs of treatment, and for the healthcare team to reduce the incidence and severity of financial burden. Current guidelines recommend clinician awareness of price variability and high costs of treatment. Clinicians are recommended to explore cost concerns and address financial worries, especially in high risk groups. Future guidelines should include advice on facilitating cost transparency discussions, with provision of cost information and resources.

Paragon (ANZGOG-0903): Phase 2 Study of Anastrozole in Women With Estrogen or Progesterone Receptor-Positive Platinum-Resistant or -Refractory Recurrent Ovarian Cancer.

BACKGROUND: There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptor-positive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer. METHODS: Postmenopausal women who had estrogen and/or progesterone receptor-positive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were eligible. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. The study was prospectively registered (ACTRN12610000796088). RESULTS: There were 49 evaluable patients, and clinical benefit was observed in 13 (27%; 95% confidence interval [CI], 16%-40%). There were no complete or partial RECIST version 1.1 responses. Clinical benefit was associated with higher global quality-of-life scores. Median progression-free survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed within 6 months. Seven patients continued on treatment for longer than 6 months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore of more than 200, but this difference was not statistically significant. CONCLUSIONS: A subset of patients with estrogen- or progesterone-positive platinum-resistant or platinum-refractory recurrent epithelial ovarian cancers derives clinical benefit from anastrozole, with acceptable toxicity. The challenge remains how to identify them.

The relationship between nutritional status, inflammatory markers and survival in patients with advanced cancer: a prospective cohort study.

BACKGROUND: Malnutrition and elevated inflammatory markers have a negative impact on clinical outcomes in cancer patients. Few studies have investigated the associations between inflammatory makers, nutritional status and survival. This study investigates the association between nutritional status, inflammatory markers and overall survival (OS) in patients with advanced cancer. METHODS: This prospective cohort study recruited 114 adult patients from January 2007 to January 2010. It included patients diagnosed with advanced cancer, good Eastern Cooperative Oncology Group (ECOG) performance status 0-2, a prognosis of more than 3 months and had not received chemotherapy for advanced cancer prior to enrollment. Baseline data were collected prior to commencement of chemotherapy. Patients were followed up from the date of baseline nutritional assessment until the date of death or the date that data were last updated, whichever came first. RESULTS: Malnourished cancer patients had statistically significant higher concentrations of serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) or modified Glasgow Prognostic Score (mGPS) prior to starting chemotherapy. In univariate analyses to predict survival, mGPS 1 or 2 had a hazard ratio (HR) of 1.81 (95 % confidence interval (CI) 1.13-2.89) and NLR ≥ 5 had a HR of 1.13 (95 % CI 1.08-4.60) and malnutrition (HR of 1.66 for Patient-Generated Subjective Global Assessment (PG-SGA) B (95 % CI 1.02-2.71), and HR for severely malnourished patients (PG-SGA C) was 2.73 (95 % CI 1.50-4.96). CONCLUSIONS: Inflammatory markers were statistically associated with malnutrition. Malnutrition and mGPS were significant independent predictors of overall survival in patients with advanced cancer.

Effect of medical Qigong on cognitive function, quality of life, and a biomarker of inflammation in cancer patients: a randomized controlled trial.

PURPOSE: Cancer patients often experience diminished cognitive function (CF) and quality of life (QOL) due to the side effects of treatment and the disease symptoms. This study evaluates the effects of medical Qigong (MQ; combination of gentle exercise and meditation) on CF, QOL, and inflammation in cancer patients. METHODS: Eighty-one cancer patients recruited between October 2007 and May 2008 were randomly assigned to two groups: a control group (n = 44) who received the usual health care and an intervention group (n = 37) who participated in a 10-week MQ program. Self-reported CF was measured by the European Organization for Research and Treatment of Cancer (EORTC-CF) and the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog). The Functional Assessment of Cancer Therapy-General (FACT-G) was used to measure QOL. C-reactive protein (CRP) was assessed as a biomarker of inflammation. RESULTS: The MQ group self-reported significantly improved CF (mean difference (MD) = 7.78, t (51) = -2.532, p = 0.014) in the EORTC-CF and all the FACT-Cog subscales [perceived cognitive impairment (MD = 4.70, t (43) = -2.254, p = 0.029), impact of perceived cognitive impairment on QOL (MD = 1.64, t (45) = -2.377, p = 0.024), and perceived cognitive abilities (MD = 3.61, t (45) = -2.229, p = 0.031)] compared to controls. The MQ group also reported significantly improved QOL (MD = 12.66, t (45) = -5.715, p < 0.001) and had reduced CRP levels (MD = -0.72, t (45) = 2.092, p = 0.042) compared to controls. CONCLUSIONS: Results suggest that MQ benefits cancer patients' self-reported CF, QOL, and inflammation. A larger randomized controlled trial including an objective assessment of CF is planned.

Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103).

PURPOSE: The primary objective of this study was to determine the recommended dose of the vascular disrupting agent, BNC105P, in combination with gemcitabine and carboplatin in patients with ovarian cancer in first or second relapse with a minimum 4 month progression-free interval after last platinum. METHODS: Patients received carboplatin AUC4 on day 1 in combination with escalating doses of 800 or 1000 mg/m2 gemcitabine on days 1 and 8 and escalating doses of 12 or 16 mg/m2 BNC105P on days 2 and 9 every 21 days for a maximum for six cycles. Maintenance treatment with 16 mg/m2 BNC105P treatment continued for a maximum of six additional cycles. Patients were followed for safety and anti-tumor activity. RESULTS: Fifteen patients were enrolled in the study. Adverse events were most commonly of hematological origin. Dose-limiting toxicities (thrombocytopenia and neutropenia) occurred in two patients at the dose level of 800 mg/m2 gemcitabine, carboplatin AUC4 and 16 mg/m2 BNC105P. No dose-limiting toxicities were observed at a dose level of gemcitabine 1000 mg/m2, carboplatin AUC4 and BNC105P 12 mg/m2. BNC105P as a single agent was well tolerated at a dose of 16 mg/m2 in maintenance treatment. Ten patients (67%) achieved a complete or partial response according to CA125 and/or RECIST response criteria, four of 13 (31%) responded by RECIST alone. The median progression-free survival was 5.9 months. CONCLUSIONS: We have established that BNC105P 12 mg/m2 with gemcitabine 1000 mg/m2 and carboplatin AUC4 is the recommended dose level and has an acceptable toxicity profile. Further exploration of BNC105P in the ovarian cancer setting is planned.

Patterns of platinum drug use in an acute care setting: a retrospective study.

PURPOSE: Platinum drugs have been in use in cancer treatment for more than 40 years, but little is known about the pattern of their use. The aim of this study was to examine the patterns of platinum drug use, with a secondary aim to describe the occurrence of dose reductions. METHODS: A retrospective analysis was conducted of oncology pharmacy dispensing records from a single hospital in Australia. Data related to drug choice, regimen and dose reductions were included in this study if the patient had received their last round of chemotherapy between November 2014 and July 2015. RESULTS: Of the 156 patients included in the study, 46% were dispensed a platinum drug during their treatment. The most commonly dispensed drugs were cisplatin (40%), carboplatin (40%) and oxaliplatin (15%), while some patients (5%) received more than one platinum drug. Dose reductions were more common in patients who were treated with a platinum drug (73%) compared with patients treated with non-platinum drugs (55%). The most common reason for a dose reduction was cytopenia. CONCLUSIONS: The findings suggest that platinum drugs remain one of the most commonly dispensed drugs to treat cancer patients and most patients receive a dose reduction during treatment.

Implementation of a lung cancer multidisciplinary team standardised template for reporting to general practitioners: a mixed-method study.

OBJECTIVES: Few interventions have been designed that provide standardised information to primary care clinicians about the diagnostic and treatment recommendations resulting from cancer multidisciplinary team (MDT) (tumour board) meetings. This study aimed to develop, implement and evaluate a standardised template for lung cancer MDTs to provide clinical information and treatment recommendations to general practitioners (GPs). Specific objectives were to (1) evaluate template feasibility (acceptability, appropriateness and timeliness) with GPs and (2) document processes of preimplementation, implementation and evaluation within the MDT setting. DESIGN: A mixed-method study design using structured interviews with GPs and qualitative documentation of project logs about implementation processes. SETTING: Two hospitals in Central Sydney, New South Wales, Australia. PARTICIPANTS: 61 GPs evaluated the template. Two lung cancer MDTs, consisting of 33 clinicians, and eight researchers participated in template development and implementation strategy. RESULTS: The MDT-reporting template appears to be a feasible way of providing clinical information to GPs following patient presentation at a lung cancer MDT meeting. Ninety-five per cent of GPs strongly agreed or agreed that the standardised template provided useful and relevant information, that it was received in a timely manner (90%) and that the information was easy to interpret and communicate to the patient (84%). Implementation process data show that the investment made in the preimplementation stage to integrate the template into standard work practices was a critical factor in successful implementation. CONCLUSIONS: This study demonstrates that it is feasible to provide lung cancer MDT treatment recommendations to GPs through implementation of a standardised template. A simple intervention, such as a standardised template, can help to address quality gaps and ensure that timely information is communicated between tertiary and primary care healthcare providers.

XANES investigation of the Co oxidation state in solution and in cancer cells treated with Co(III) complexes.

XANES spectroscopy has been used to investigate whether it is possible to determine the oxidation state and coordination environment of Co complexes following treatment of cancer cells with Co(III) or Co(II) complexes. Our results show that the variation of the XANES with coordination geometry make it impossible to do this in a completely reliable way which is in contrast to the situation for platinum and chromium. It was established that the XANES spectrum obtained from cells treated with [Co(diNOsar)]Br(3) remained unchanged with respect to its XANES spectrum obtained in solution, demonstrating that the [Co(diNOsar)]Br(3) complex remained intact after 24h in cellular media (diNOsar=1,8-dinitro-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane). In contrast, the XANES spectra obtained from cells treated with Na[Co(acac)(3)] and [Co(acac)(3)] differed from the XANES spectra of the respective complexes obtained in solution, indicating a change in co-ordination environment for both complexes upon uptake in cells. The similarity of these spectra suggests that appearance of this XANES can be used as an indication of loss of the carrier ligands, a useful indicator in the study of hypoxia selective complexes. The results obtained for Na[Co(acac)(3)] and [Co(acac)(3)] are consistent with the intracellular coordination of cobalt(III) to sulfur ligands upon cellular uptake.

The mechanism of action of platinum(IV) complexes in ovarian cancer cell lines.

The reduction potentials, lipophilicities, cellular uptake and cytotoxicity have been examined for two series of platinum(IV) complexes that yield common platinum(II) complexes on reduction: cis-[PtCl(4)(NH(3))(2)], cis,trans,cis-[PtCl(2)(OAc)(2)(NH(3))(2)], cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)], [PtCl(4)(en)], cis,trans-[PtCl(2)(OAc)(2)(en)] and cis,trans-[PtCl(2)(OH)(2)(en)] (en=ethane-1,2-diamine, OAc=acetate). As previously reported, the reduction occurs most readily when the axial ligand is chloride and least readily when it is hydroxide. The en series of complexes are marginally more lipophilic than their ammine analogues. The presence of axial chloride or acetate ligands results in a slighter higher lipophilicity compared with the platinum(II) analogue whereas hydroxide ligands lead to a substantially lower lipophilicity. The cellular uptake is similar for the platinum(II) species and their analogous tetrachloro complexes, but is substantially lower for the acetato and hydroxo complexes, resulting in a correlation with the reduction potential. The activities are also correlated with the reduction potentials with the tetrachloro complexes being the most active of the platinum(IV) series and the hydroxo being the least active. These results are interpreted in terms of reduction, followed by aquation reducing the amount of efflux from the cells resulting in an increase in net uptake.

The median informs the message: accuracy of individualized scenarios for survival time based on oncologists' estimates.

PURPOSE: To determine the accuracy and usefulness of oncologists' estimates of survival time in individual patients with advanced cancer. PATIENTS AND METHODS: Twenty-one oncologists estimated the "median survival of a group of identical patients" for each of 114 patients with advanced cancer. Accuracy was defined by the proportions of patients with an observed survival time bounded by prespecified multiples of their estimated survival time. We expected 50% to live longer (or shorter) than their oncologist's estimate (calibration), 50% to live from half to double their estimate (typical scenario), 5% to 10% to live ≤ one quarter of their estimate (worst-case scenario), and 5% to 10% to live three or more times their estimate (best-case scenario). Estimates within 0.67 to 1.33 times observed survival were deemed precise. Discriminative value was assessed with Harrell's C-statistic and prognostic significance with proportional hazards regression. RESULTS: Median survival time was 11 months. Oncologists' estimates were relatively well-calibrated (61% shorter than observed), imprecise (29% from 0.67 to 1.33 times observed), and moderately discriminative (Harrell C-statistic 0.63; P = .001). The proportion of patients with an observed survival half to double their oncologist's estimate was 63%, ≤ one quarter of their oncologist's estimate was 6%, and three or more times their oncologist's estimate was 14%. Independent predictors of observed survival were oncologist's estimate (hazard ratio [HR] = 0.92; P = .004), dry mouth (HR = 5.1; P < .0001), alkaline phosphatase more than 101 U/L (HR = 2.8; P = .0002), Karnofsky performance status ≤ 70 (HR = 2.3; P = .007), prostate primary (HR = 0.23; P = .002), and steroid use (HR = 2.4; P = .02). CONCLUSION: Oncologists' estimates of survival time were relatively well-calibrated, moderately discriminative, independently associated with observed survival, and a reasonable basis for estimating worst-case, typical, and best-case scenarios for survival.

Supporting treatment decision making in advanced cancer: a randomized trial of a decision aid for patients with advanced colorectal cancer considering chemotherapy.

PURPOSE: Decision making in advanced cancer is increasingly complex. We developed a decision aid (DA) for patients with advanced colorectal cancer who are considering first-line chemotherapy and reviewing treatment options, prognostic information, and toxicities. We examined its impact on patient understanding, treatment decisions, decisional conflict, decision making, consultation satisfaction, anxiety, and quality of life by using a randomized trial design. PATIENTS AND METHODS: In all, 207 patients with colorectal cancer who were considering first-line chemotherapy for metastatic disease were randomly assigned to receive a standard medical oncology consultation or a consultation in which the DA (take-home booklet with audio recording, reviewed by an oncologist) was used. Participants completed questionnaires postconsultation, postdecision, and 1 month later. RESULTS: In this study, 100 patients were randomly assigned to the control arm, and 107 received the DA. Median age of the sample was 62 years, 58% were male, 89% had a performance status of 0 or 1, and 36% had received prior adjuvant chemotherapy. Patients receiving the DA demonstrated a greater increase in understanding of prognosis, options, and benefits, with higher overall understanding (P < .001). Decisional conflict, treatment decisions, and achievement of involvement preferences were similar between the groups. Anxiety was similar across groups and decreased over time. Most patients were confident in a decision during the first consultation; 74% chose chemotherapy, 7% supportive care alone, and 10% observation. CONCLUSION: This randomized trial of a decision aid in advanced cancer showed that its use in advanced colorectal cancer improved patient understanding of prognosis, treatment options, risks, and benefits without increasing anxiety. DAs can improve informed consent and can be tested through randomized trials even in the advanced cancer setting.

Synthesis, characterisation and in vitro cytotoxicity studies of a series of chiral platinum(II) complexes based on the 2-aminomethylpyrrolidine ligand: X-ray crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr=N-dimethyl-2(R)-aminomethylpyrrolidine).

A series of platinum(II) complexes were synthesised based on the enantiomerically pure amino acid proline. Novel synthetic pathways were developed, adapted from standard peptide chemistry, to produce the 2-aminomethylpyrrolidine (pyrr) ligand and its derivatives with differing arrangements of methyl substituents at the exocyclic amine sites. The crystal structure of [PtCl(2)(R-dimepyrr)] (R-dimepyrr=N,N-dimethyl-2(R)-aminomethylpyrrolidine) is reported and the five-membered ligand ring has been shown to be in an envelope conformation. Cytotoxicity studies were carried out on the ovarian cancer A2780 tumour cell line and its cisplatin-resistant variant, A2780cisR. Remarkably good activity was seen for several of the drugs when compared to cisplatin despite the addition of substantial steric bulk to the amine groups, and there was a lack of cross-resistance with cisplatin seen for some compounds.

Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial.

GOALS: The aim of the study was to assess the impact of an eicosapentanoic acid-containing protein and energy dense oral nutritional supplement (EPA-ONS) on nutritional and inflammatory status, quality of life (QOL), plasma phospholipids (PPL) and cytokine profile, tolerance of irinotecan-containing chemotherapy and EPA-ONS in patients with advanced colorectal cancer (CRC) receiving chemotherapy. MATERIALS AND METHODS: Patients with advanced CRC having one prior chemotherapy regimen received 480 ml of EPA-ONS daily for 3 weeks before commencing chemotherapy with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI), and continued for 3 cycles of treatment (9 weeks). All assessments including weight, body composition, C-reactive protein (CRP), QOL, dietary intake, PPL and cytokine analyses were performed at baseline, 3 and 9 weeks. RESULTS: Twenty-three patients were enrolled, 20 completed 3 weeks, and 15 completed 9 weeks. The mean EPA-ONS intake was 1.7 tetrapaks (408 ml) daily. There was a significant increase in mean weight (2.5 kg) at 3 weeks (p=0.03). Lean body mass (LBM) was maintained. Protein and energy intake significantly decreased after the commencement of chemotherapy (protein p=0.003, energy p=0.02). There was a significant increase in energy levels (p=0.03), whilst all other QOL measures were maintained. PPL EPA levels increased significantly over the first 3 weeks. Mean CRP increased by 14.9 mg/L over the first 3 weeks (p=0.004), but decreased to baseline levels by the end of the trial. There was a significant correlation between plasma IL-6 and IL-10 concentrations and survival, and between IL-12 and toxicity. CONCLUSION: Dietary counseling and the provision of EPA-ONS may result in maintenance of nutritional status and QOL, however randomized trials are required to evaluate the impact of EPA on toxicity from chemotherapy.

Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial.

BACKGROUND: Depression, anxiety, fatigue, and impaired wellbeing are common, important, and closely related in advanced cancer. We aimed to identify the effects of an established antidepressant on these symptoms and survival in patients with advanced cancer who did not have major depression as assessed by clinicians. METHODS: Between July, 2001, and February, 2006, 189 patients with advanced cancer were randomly assigned sertraline 50 mg (n=95), or placebo (n=94), once per day. The primary outcome was depression as assessed by the Centre for Epidemiologic Studies Depression scale (CES-D); the main secondary outcomes were: anxiety as assessed by Hospital Anxiety and Depression Scales (HADS-A); overall quality of life and fatigue as assessed by Functional Assessment of Cancer Therapy General and Fatigue scales (FACT-G and FACT-F, respectively); and clinicians' ratings of quality of life by use of Spizter's Quality of Life Index (SQLI). Multiple measures were used for corroboration of the most important outcomes. Primary analyses were done by intention to treat and were based on scale scores at 4 weeks and 8 weeks. The benefits of sertraline compared with placebo are expressed on a range from +100 (ie, maximum benefit) to -100 (ie, maximum harm); a difference of 10 was deemed clinically significant. This clinical trial is registered at Current Controlled Trials website http://www.controlled-trials.com/ISRCTN72466475. FINDINGS: Sertraline had no significant effect (scale, benefit over placebo [95% CI]) on depression (CES-D 0.4 [-2.6 to 3.4]), anxiety (HADS-A 2.0 [-1.5 to 5.5]), fatigue (FACT-F 0.3 [-4.3 to 4.9]), overall quality of life (FACT-G 1.7 [-1.3 to 4.7]), or clinicians' ratings (SQLI 2.0 [-2.5 to 6.5]), and the 95% CI ruled out a clinically significant benefit for all main outcomes. Sertraline was discontinued more often and earlier than was placebo (hazard ratio 1.46 [1.03-2.06], p=0.03). Recruitment was stopped after the first planned interim analysis in February 2006 (n=150) showed that survival was longer in patients assigned placebo than in patients assigned sertraline (unadjusted hazard ratio 1.60 [95% CI 1.04-2.45], log-rank p=0.04; adjusted hazard ratio 1.62 [1.06-2.41], Cox model p=0.02). However, at the final analysis in July 2006 of all patients (n=189) and with longer follow-up, survival did not differ significantly between the treatment groups (unadjusted hazard ratio 1.35 [0.95-1.91], log-rank p=0.09; adjusted hazard ratio 1.27 [0.87-1.84], Cox model p=0.20). The trial was closed because it had ruled out a significant benefit of sertraline. INTERPRETATION: Sertraline did not improve symptoms, wellbeing, or survival in patients with advanced cancer who do not have major depression, and should be reserved for those with a proven indication.

Evaluation of nutritional and inflammatory status of advanced colorectal cancer patients and its correlation with survival.

The purpose of this study was to evaluate novel inflammatory and nutritional prognostic factors in patients with advanced colorectal cancer (ACRC). All ACRC patients attending the clinic for palliative treatment were eligible for study. Demographics, including performance status (PS), C-reactive protein (CRP), albumin (Alb), Glasgow prognostic score (GPS), weight, weight history, body mass index (BMI), and nutritional status using the patient-generated subjective global assessment (PGSGA), were collected and correlated with survival. At a median follow-up of 29.8 mo, with a minimum follow-up of 15.7 mo, the median survival was 9.9 mo (0.8-21.8 mo). Fifteen (29%) patients were newly diagnosed (stage IV colorectal cancer), and 36 (71%) had received prior chemotherapy. Although the median BMI was 27 kg/m2 (range = 17-41 kg/m2), 28 of 50 (56%) were nutritionally at risk. In fact, 19 patients (38%) were critically in need of nutrition intervention (PGSGA score of > or =9). Thirty-three of 48 patients (69%) had an elevated CRP (>10 mg/l with a median of 21.1 mg/L), and 7 patients (15%) had both a CRP of >10 mg/l and hypoalbuminemia (< 35 g/l). A significant positive correlation was found between PGSGA score and CRP (P = 0.003; r = 0.430). Using univariate analysis, significantly worse survival was found for patients with poorer PS (P = 0.001), high GPS (P = 0.04), low Alb (P = 0.017), elevated serum alkaline phosphatase (SAP; P = 0.018), PGSGA score of > 9 (P = 0.001), and PGSGA group B/C (P = 0.02). Using the Cox proportional hazard model for multivariate survival analysis, type of treatment (hazard ratio, HR = 1.48; 95% confidence interval, CI = 1.11-1.79; P = 0.005), PS (HR = 2.37; 95% CI = 1.11-5.09; P = 0.026), GPS (HR = 2.27; 95% CI = 1.09-4.73; P = 0.028), and SAP (HR = 0.44; 95% CI = 0.18-1.07; P =0.069) remained significant predictors of survival. These preliminary data suggest that the type of treatment, PS, GPS, and SAP are important predictors of survival in ACRC.

The fate of platinum(II) and platinum(IV) anti-cancer agents in cancer cells and tumours.

SRIXE mapping has been used to gain insight into the fate of platinum(II) and platinum(IV) complexes in cells and tumours treated with anticancer active complexes to facilitate the development of improved drugs. SRIXE maps were collected of thin sections of human ovarian (A2780) cancer cells treated with bromine containing platinum complexes, cis-[PtCl(2)(3-Brpyr)(NH(3))] (3-Brpyr=3-bromopyridine) and cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] (OAcBr=bromoacetate), or a platinum complex with an intercalator attached cis-[PtCl(2)(2-[(3-aminopropyl)amino]-9,10-anthracenedione)(NH(3))]. After 24h the complexes appear to be localised in the cell nucleus with a lower concentration in the surrounding cytoplasm. In cells treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] the concentration of bromine was substantially higher than in control cells and the bromine was co-localised with the platinum consistent with the 3-bromopyridine ligand remaining bound to the platinum. The cells treated with cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] also showed an increased level of bromine, but to a much lesser extent than for those treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] suggestive of substantial reduction of the platinum(IV) complex. Maps were also collected from thin sections of a 4T1.2 neo 1 mammary tumour xenograft removed from a mouse 3h after treatment with cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)] and revealed selective uptake of platinum by one cell.

XANES determination of the platinum oxidation state distribution in cancer cells treated with platinum(IV) anticancer agents.

Here we describe the use of X-ray absorption near edge spectroscopy (XANES) to provide information about the relative proportions of platinum(II) and platinum(IV) complexes by analyzing the XANES edge height. The intracellular reduction of platinum(IV) complexes in cancer cells has been observed directly, and the proportion of reduction after 2 h was found to correlate with the reduction potentials of the complexes.

Overexpression of BclXL in a human ovarian carcinoma cell line: paradoxic effects on chemosensitivity in vitro versus in vivo.

The effect of overexpressing the antiapoptotic protein BclXL in a human ovarian carcinoma cell line has been investigated in terms of sensitivity to the 2 major drugs used to treat this disease, paclitaxel and cisplatin. Stable transfection of BclXL into CH1 cells, which are relatively sensitive to cisplatin, resulted in around 2.7-fold higher expression in comparison with empty vector controls. However, this level of overexpression did not result in significant resistance in vitro to paclitaxel or cisplatin at the 50% inhibition level, using either short-term (4-day) growth inhibition or longer term colony-forming assays. By contrast, parallel subcutaneous xenograft models of these isogenic ovarian carcinoma cells in vivo, differing only in BclXL status, showed that this low-level BclXL overexpression conferred significant resistance to both paclitaxel and cisplatin in comparison with parent, nontransfected tumours. Whereas parent non-BclXL transfected tumours were highly responsive, with the disappearance of tumours for at least 50 days post treatment, tumours overexpressing BclXL grew back after 30 and 20 days after treatment with paclitaxel and cisplatin, respectively. These differences in responsiveness to paclitaxel in vivo were not attributable to any significant changes in the delivery of drug to the tumour. These data suggest that the responsiveness of ovarian cancer to paclitaxel and cisplatin in vivo, and therefore perhaps clinically, is influenced by levels of the antiapoptotic protein BclXL. Such effects may be missed in vitro when using short-term growth inhibition or clonogenic assays.