Strengths and limitations of computer assisted telephone interviews (CATI) for nutrition data collection in rural Kenya.

Despite progress in fighting undernutrition, Africa has the highest rates of undernutrition globally, exacerbated by drought and conflict. Mobile phones are emerging as a tool for rapid, cost effective data collection at scale in Africa, as mobile phone subscriptions and phone ownership increase at the highest rates globally. To assess the feasibility and biases of collecting nutrition data via computer assisted telephone interviews (CATI) to mobile phones, we measured Minimum Dietary Diversity for Women (MDD-W) and Minimum Acceptable Diet for Infants and Young Children (MAD) using a one-week test-retest study on 1,821 households in Kenya. Accuracy and bias were assessed by comparing individual scores and population prevalence of undernutrition collected via CATI with data collected via traditional face-to-face (F2F) surveys. We were able to reach 75% (n = 1366) of study participants via CATI. Women's reported nutrition scores did not change with mode for MDD-W, but children's nutrition scores were significantly higher when measured via CATI for both the dietary diversity (mean increase of 0.45 food groups, 95% confidence interval 0.34-0.56) and meal frequency (mean increase of 0.75 meals per day, 95% confidence interval 0.53-0.96) components of MAD. This resulted in a 17% higher inferred prevalence of adequate diets for infants and young children via CATI. Women without mobile-phone access were younger and had fewer assets than women with access, but only marginally lower dietary diversity, resulting in a small non-coverage bias of 1-7% due to exclusion of participants without mobile phones. Thus, collecting nutrition data from rural women in Africa with mobile phones may result in 0% (no change) to as much as 25% higher nutrition estimates than collecting that information in face-to-face interviews.

Metastatic primary adenocarcinoma of the bladder in a twenty-five years old woman.

Primary adenocarcinoma of the bladder is a rare tumor. The classification between primary vesical and urachal is debated. We present the case of a young female who presented clinicopathological features of a metastatic urachal adenocarcinoma, but the histological result revealed primary adenocarcinoma of the bladder contrary to expectancy. To the best of our knowledge this is the first reported case of a metastatic adenocarcinoma of the bladder in a 25 years old female. This case emphasizes the challenge for urologists to recognize and manage this aggressive tumor in the setting described.

A phase I study of the oral platinum agent satraplatin in sequential combination with capecitabine in the treatment of patients with advanced solid malignancies.

BACKGROUND: The broad spectrum of antitumor activity of both the oral platinum analogue satraplatin (S) and capecitabine (C), along with the advantage of their oral administration, prompted a clinical study aimed to define the maximum tolerated dose (MTD) of the combination. PATIENTS AND METHODS: Four dose levels of S (mg/m(2)/day) and C (mg/m(2)/day) were evaluated in adult patients with advanced solid tumors: 60/1650, 80/1650, 60/2000, 70/2000; a course consisted of 28 days with sequential administration of S (days 1-5) and C (days 8-21) followed by one week rest. RESULTS: Thirty-seven patients were treated, 24 in the dose escalation and 13 in the expansion phase; at the MTD, defined at S 70/C 2000, two patients presented dose limiting toxicities: lack of recovery of neutropenia by day 42 and nausea with dose skip of C. Most frequent toxicities were nausea (57%), diarrhea (51%), neutropenia (46%), anorexia, fatigue, vomiting (38% each). Two partial responses were observed in platinum sensitive ovarian cancer and one in prostate cancer. CONCLUSION: At S 70/C 2000 the combination of sequential S and C is tolerated with manageable toxicities; its evaluation in platinum and fluorouracil sensitive tumor types is worthwhile because of the easier administration and lack of nephro- and neurotoxicity as compared to parent compounds.

[New drugs at the horizon for men with prostate cancer]. / Quels nouveaux médicaments a l'horizon pour te traitement du cancer avancé de la prostate?

Despite major progress in the understanding of biological mechanisms underlying metastatic prostate cancer, the treatment of men with advanced prostate cancer remains challenging. Several randomized controlled trials with promising or positive results are underway or just released. Here we discuss new treatments which might be used in clinic in the near future: hormonal treatments (Abiraterone and MDV3100), a new chemotherapy (Cabazitaxel), a cellular vaccine (Sipuleucel-T), anti-angiogenic drugs (Bevacizumab, Aflibercept), a new radioactive treatment (Alpharadin) and a new bone-protective agent (Deno-sumab).

Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001.

PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.

[Breast cancer: pathology, the cornerstone of therapeutic decision]. / Cancer du sein : la pathologie, pierre angulaire de la décision therapeutique.

Tailoring adjuvant therapy in breast cancer patients relies on prognostic and predictive factors, most of which are currently established by histopathological analysis of tumors. The quality of the assessment of the former (i.e.: tumor size, lymph node status, tumor grade, HER2 status, and lymphovascular invasion) and the latter (estrogen and progesteron receptors expression, HER2 overexpression or amplification) is an essential prerequisite for an optimal therapeutic decision. If the prognostic and predictive values of multigenes signatures are confirmed by on-going clinical studies, this approach could enter the clinical practice in the coming years and result in improved accuracy of adjuvant therapies in breast cancer patients. This approach might especially allow avoiding overtreatment in patients at low risk of recurrence.

Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group.

PURPOSE: This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent. RESULTS: A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. CONCLUSION: GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

A phase II, open-label study of gefitinib (IRESSA) in patients with locally advanced, metastatic, or relapsed renal-cell carcinoma.

Epidermal growth factor receptor (EGFR) expression has been associated with clinical outcome in some studies of renal-cell carcinoma (RCC). We investigated the efficacy and safety of gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, in RCC patients. This phase II trial recruited 28 patients with advanced, metastatic, or relapsed RCC. Patients received oral gefitinib 500 mg/day. Objective responses (ORs) were assessed every 2 months according to RECIST. Baseline tumor biopsies were analyzed immunohistochemically for EGFR expression. At trial closure (March 2003), no ORs were seen but 14 patients (53.8%) had stable disease. At extended analysis (August 2004), median time to progression was 110 days (95% confidence interval [CI]: 55, 117); median overall survival was 303 days (95% CI 180, 444). Gefitinib was generally well tolerated. Skin rash and diarrhea were the most common drug-related adverse events (AEs) [54 and 39% of patients, respectively] and the most common drug-related grade 3/4 AEs (both 11%). The majority of tumor biopsies (91%) had > or =70% of tumor cells expressing membrane EGFR. Despite the lack of ORs in this study, disease control was observed in 53.8% of patients. Gefitinib was generally well tolerated and no unexpected drug-related AEs were observed.

Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy.

Anti-angiogenic therapies are currently in cancer clinical trials, but to date there are no established tests for evaluating the angiogenic status of a patient. We measured 11 circulating angiogenesis-associated molecules in cancer patients before and after local treatment. The purpose of our study was to screen for possible relationships among the different molecules and between individual molecules and tumor burden. We measured VEGF-A, PlGF, SCF, MMP-9, EDB+ -fibronectin, sVEGFR-2, sVEGFR-1, salphaVbeta3, sTie-2, IL-8 and CRP in the blood of 22 healthy volunteers, 17 early breast, 17 early colorectal, and 8 advanced sarcoma/melanoma cancer patients. Breast cancer patients had elevated levels of VEGF-A and sTie-2, colorectal cancer patients of VEGF-A, MMP-9, sTie-2, IL-8 and CRP, and melanoma/sarcoma patients of sVEGFR-1. salphaVbeta3 was decreased in colorectal cancer patients. A correlation between VEGF-A and MMP-9 was found. After tumor removal, MMP-9 and salphaVbeta3 significantly decreased in breast and CRP in colorectal cancer, whereas sVEGFR-1 increased in colorectal cancer patients. In sarcoma/melanoma patients treated regionally with TNF and chemotherapy we observed a rise in VEGF-A, SCF, VEGFR-2, MMP-9, Tie-2 and CRP, a correlation between CRP and IL-8, and a decreased in sVEGFR-1 levels. In conclusion, among all factors measured, only VEGF-A and MMP-9 consistently correlated to each other, elevated CRP levels were associated with tumor burden, whereas sVEGF-R1 increased after tumor removal in colorectal cancer. Treatment with chemotherapy and TNF induced changes consistent with an angiogenic switch. These results warrant a prospective study to compare the effect of surgical tumor removal vs. chemotherapy on some of these markers and to evaluate their prognostic/predictive value.

[Cancer screening: when and how?]. / Le dépistage du cancer.

Advances in cancer biology have led to the development of screening tests that allow an early diagnosis. Cancer screening is not just the matter of a single individual patient, it is a matter of public health. Screening is commonly viewed as of no harm, when in fact harms are associated with the majority of cancer screening tests. A test should only be used when the potential of benefit clearly outweighs the risks for harm. The data in the literature are not always clear cut and in a lot of cases guidelines are somewhat controversial. What is known and what is unknown about screening tests is quite different from what is believed by the public. The aim of this work is to summarize the different methods and guidelines in cancer screening to help choosing the right test at the right time for the right person.

[Dangerous liaisons: relation between oncologist and general practitioner]. / Les liaisons dangereuses: interactions entre médecins de premier recours et oncologues médicaux.

Due to the nature of the disease, patients often have a privileged and close relationship with their oncologist, and the oncologist also with their patients. This may in turn be detrimental to the relation between the general practitioner and the patient. Patients will not return to their general practitioner until end of life care or a consultation at the patient's home if necessary. In order to maintain a balance between the caretakers and assure appropriate involvement of the family physician, continuous communication and exchange of information are essential. This review identifies some of the problems and potential conflicts, which may arise, and discusses how the interaction could be improved.

Synthesis and SAR of 2-carboxylic acid indoles as inhibitors of plasminogen activator inhibitor-1.

We synthesized and evaluated a novel series of 2-carboxylic acid indole-based inhibitors of plasminogen activator inhibitor-1 (PAI-1). Systematic modification of the N-1 position and the 5-position of the indole scaffold resulted in the identification of several compounds that showed good potency against PAI-1 in the spectrophotometric assay. This potency did not always translate to the antibody assay. Solubility and serum protein binding studies on selected analogs revealed that protein binding might be a factor in the poor correlation between the two assays.

Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails.

PURPOSE: To assess the efficacy and toxicity of the marine-derived alkaloid trabectedin (ET-743) in patients with advanced ovarian cancer refractory to or experiencing disease relapse after platinum- and taxane-based chemotherapy. PATIENTS AND METHODS: Fifty-nine patients from four institutions either resistant (n = 30) or sensitive (n = 29) to prior platinum and taxanes were treated with a 3-hour infusion of trabectedin every 3 weeks. Patients were monitored weekly for toxicity and restaged every two cycles for response. Response was assessed according to Response Evaluation Criteria in Solid Tumors Group. RESULTS: The peer-reviewed objective response rate in platinum-sensitive patients was 43% (95% CI, 23% to 65%) with an estimated median time to progression of 7.9 months (95% CI, 7.5 to 14.1 months); in platinum-resistant patients two partial responses were observed. Responses were durable for up to 12.9 months (median, 5 months). The predominant toxicities at the recommended dose of 1,300 microg/m(2) were neutropenia, asthenia, and self-limited increase of aminotransferases never requiring treatment interruption. CONCLUSION: Trabectedin administered as a 3-hour infusion at 1,300 microg/m(2) is a safe new drug with promising activity in relapsed ovarian cancer, showing a 43% objective response rate in patients with platinum-sensitive disease, which favorably compares with other salvage treatments and warrants additional development either alone or in combination.

Acquired hemophilia as first manifestation of breast carcinoma in a man under long-term spironolactone therapy.

A 69-year-old man under long-term spironolactone therapy (16 years) was hospitalized with spontaneous hematoma on the trunk and extremities. Coagulation studies disclosed an acquired hemophilia that was successfully treated with human factor VIII for a few days and immunosuppressive agents for several months. Physical examination revealed bilateral gynecomastia and an upper left quadrant breast nodule. Complete staging was unremarkable. Complete left mastectomy was performed. Histopathology showed invasive ductal carcinoma, expressing positivity for estrogen and progesterone receptors. The acquired hemophilia was considered to be a paraneoplasic syndrome. The question of a linkage between long-term spironolactone therapy and breast carcinoma is discussed.

WAY-140312 reduces plasma PAI-1 while maintaining normal platelet aggregation.

Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of tissue plasminogen activator (tPA) and is elevated in diseases of vascular remodeling. In this study, we describe an inhibitor of active PAI-1, WAY-140312. Using fluorescence spectroscopy, it was determined that WAY-140312 bound PAI-1 at a single binding site with a dissociation constant of 5 microM. In a biochemical assay determining direct tPA activity, human recombinant PAI-1 completely inhibited tPA, but this inhibition was blocked by WAY-140312 at an IC(50) of 15.6 microM. In vivo, a 10 mg/kg oral dose of WAY-140312 to rats produced a significant plasma reduction of active PAI-1. Bleeding time, thrombin clotting time, and ex vivo platelet aggregation induced by ADP (20 microM) or collagen (2.5 microg/ml) were not affected by administration of WAY-140312. These results are the first to demonstrate that an orally active PAI-1 inhibitor can reduce plasma PAI-1 activity while maintaining normal platelet aggregation and coagulation.

Pharmacokinetics of satraplatin (JM216), an oral platinum (IV) complex under daily oral administration for 5 or 14 days.

BACKGROUND: Satraplatin (JM216; bis-acetatoammine-dichlorocyclohexylamine platinum (IV)) is a platinum (Pt) complex developed in an attempt to circumvent tumour resistance and which can be administered by the oral route. The fate of platinum delivered by this oral formulation administered at various doses under the 5 or 14 days schedule, has been studied to a limited extent. PATIENTS AND METHODS: Total (Ptot) and ultrafilterable (PtUF) platinum were determined in 19 patients enrolled in phase I (PI) and II (PII) studies (PI, n = 14, advanced cancer; PII, n = 5, untreated small cell lung carcinoma). JM216 doses were 10 to 50 mg m-2 day-1 x 14 d (days) (dose escalation in PI) and 120 mg m-2 day-1 x 5d (fixed dose in PII), administered to fasted patients in a standardized way. Ptot and PtUF levels were determined by atomic absorption spectrometry on d1 and d14, followed over 28 days in PI; and on d1, followed over 5 days in PII. Pharmacokinetic parameters were derived by a noncompartmental approach. RESULTS: JM216 is rapidly absorbed with a Tmax obtained within 2.5-3 hours and 1-2 hours for Ptot and PtUF, respectively. The pharmacokinetics of JM216 was linear across the tested doses in PI, with the exposure of Ptot on d14 being better correlated with dose per BSA (Body surface area) (r = 0.91) than that of PtUF (r = 0.61). In PI, Cmax on d1 increased proportionally to the dose (r = 0.82 and r = 0.72 for Ptot and PtUF, respectively). Apparent clearances in PI were 1.1 +/- 0.5 L h-1 and 37.0 +/- 33 L h-1 for Ptot and PtUF, respectively. Prolonged terminal half-lives were observed after the last JM216 administration with mean values of 216 +/- 37 hours and 107 +/- 89 hours, for Ptot and PtUF respectively. The accumulation ratio (Cmaxd14/Cmaxd1) indicated a higher accumulation of Ptot (3.5 +/- 1.6) than of PtUF (1.8 +/- 1) under multiple dose regimen. The apparent volumes of distribution (terminal phase) were similar in the PI and PII studies: 326 +/- 112 L and 3094 +/- 1493 L, and 557 +/- 267 L and 4154 +/- 2147 L, for Ptot and PtUF, respectively. In PI, the nadir of thrombocytopenia was related both to the cumulated dose of JM216 (r = 0.81) and to the AUC of Ptot on d14 (r = 0.77), whereas the AUC of PtUF was not predictive (r = 0.48). The Cmax of Ptot and PtUF on d1 was related to neutropenia (r = 0.61 and r = 0.65, respectively) and to thrombocytopenia (r = 0.77 and r = 0.74, respectively). No relationships were found between leukocytes or neutrophils percent decrease and the AUCs or total, dose of JM216. CONCLUSION: JM216 is an orally bioavailable platinum-containing chemotherapeutic agent yielding predictable total levels of platinum which appears to accumulate in plasma after multiple administration over 14 days. These results should be set in relation to clinical efficacy and tolerance, to optimise the dose regimen of JM216 in further studies.