Economic evaluations of cancer immunotherapy: a systematic review and quality evaluation.

OBJECTIVES: Scientific advances in the last decade have highlighted the use of immunotherapy, especially immune checkpoint inhibitors, to be an effective strategy in cancer therapy. However, these immunotherapeutic agents are expensive, and their use must take into account economic criteria. Thus, the objective of the present study was to systematically identify and review published EE related to the use of ipilimumab, nivolumab or pembrolizumab in melanoma, lung cancer, head and neck cancer or renal cell carcinoma, and to assess their quality. METHODS: The systematic literature research was conducted on Medline via PubMed and the Cochrane Central Register of Controlled Trials to identify economic evaluations published before July 2018. The quality of each selected economic evaluation was assessed by two independent reviewers using the Drummond checklist. RESULTS: Our systematic review was based on 32 economic evaluations using different methodological approaches, different perspectives and different time horizons. Three-quarters of the economic evaluations are full (n = 24) with a Drummond score ≥ 7, synonymous of "high quality". Among them, 66% reported a strategy that was cost-effective. The most assessed immunotherapeutic agent was nivolumab. In patients with renal cell carcinoma or head and neck cancer, it was less likely to be cost-effective than in patients with melanoma or lung cancer. CONCLUSIONS: Whether or not these findings will be confirmed remains to be seen when market approval to cover more indications is extended and new effective immunotherapeutic agents become available.

A Phase II Study Evaluating the Interest to Combine UCPVax, a Telomerase CD4 TH1-Inducer Cancer Vaccine, and Atezolizumab for the Treatment of HPV Positive Cancers: VolATIL Study.

Background: There is a strong rational of using anti-programmed cell death protein-1 and its ligand (anti-PD-1/L1) antibodies in human papillomavirus (HPV)-induced cancers. However, anti-PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti-PD-1/L1 is therefore of interest. Combining anti-PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non-small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers. Methods: Patients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously. Discussion: Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti-PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT03946358.

Duration: escalation study of oral etoposide with carboplatin in patients with varied solid tumors.

Prolonged fractionated oral administration of etoposide may present a theoretical advantage over intravenous administration of the bolus. This phase I trial was carried out to determine the recommended duration of oral etoposide in combination with a fixed dose of carboplatin. Nineteen patients with varied solid tumors, who were not candidates for standard chemotherapy, were administered an escalating duration (6, 9 or 12 consecutive days) of oral etoposide (a 25 mg capsule three times daily) combined with carboplatin AUC5 administered on day 1, by a 30 min intravenous infusion, to define the maximum tolerated dose on the basis of the acute toxicities that were reported. Etoposide was started on day 2; the cycles repeated every 28 days until disease progression or toxicity. Pharmacokinetics was carried out during the two first cycles. The maximum tolerated dose was determined to be the 12-day treatment level, with two cases of grade 4 neutropenia, grade 3 anemia and thrombocytopenia. As no severe toxicity occurred with the 9-day treatment level and in an attempt to explore an optimal combination, a new 10-day treatment plan was studied in three patients. As one patient presented dose-limiting toxicity at that level, five additional patients were included to establish the recommended regimen. Nonhematological toxicities among all patients were moderate, consisting of grade 2 nausea and asthenia. No treatment-related death occurred. Objective responses were observed in four patients and stabilization in three patients. Pharmacokinetics highlighted no interaction between etoposide and carboplatin. Fractionated oral etoposide (3×25 mg/day) for 10 days in combination with carboplatin AUC 5 presents acceptable toxicity and efficacy. The main toxicity remains hematological.

[Systemic treatment of locally advanced or metastatic penile cancer]. / Traitement systémique du cancer du pénis localement avancé ou métastatique.

Penile cancers are rare, the vast majority is represented by squamous cell carcinoma, with HPV virus being found in 30 to 40% of cases. At a locally advanced or metastatic stage, first-line treatment relies on platinum and taxane based polychemotherapy. The prognosis for advanced or metastatic penile cancer remains poor, with overall survival ranging from 13.9 to 17.1 months. After the first line, guidelines recommend various chemotherapy treatments or targeted anti-EGFR therapies whose results as well as the level of evidence are limited. A better understanding of the oncogenic pathways involved in penile cancer and a frequent expression of PD-L1 are the rationale for the elaboration of new strategies. This review article presents the data, guidelines and ongoing studies in locally advanced or metastatic penile cancer.

Open-label, randomized multicentre phase II study to assess the efficacy and tolerability of sunitinib by dose administration regimen (dose modification or dose interruptions) in patients with advanced or metastatic renal cell carcinoma: study protocol of the SURF trial.

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor approved in the first-line metastatic renal cell carcinoma (MRCC) setting at the dose of 50 mg daily for 4 weeks followed by a pause of 2 weeks. Due to toxicity, this standard schedule (50 mg daily 4/2) can induce up to 50% of sunitinib dose modification (reduction and/or interruption). The current recommendation in such case is to reduce the dose to 37.5 mg per day (standard schedule 4/2). Recent data highlight an alternative schedule: 2 weeks of treatment followed by 1 week of pause (experimental schedule 2/1). The SURF trial is set up to evaluate prospectively experimental schedule 2/1 when toxicity occurs. This article displays the key elements of the study protocol. METHODS/DESIGN: SURF [NCT02689167] is a prospective, randomized, open-label phase IIb study. Patients are included at sunitinib initiation while receiving standard schedule 4/2 (50 mg daily) according to the marketing authorization indication. When a dose adjustment of sunitinib is required, patients are randomized between standard schedule 4/2 (37.5 mg daily) and experimental schedule 2/1 (50 mg daily). Key eligibility criteria are the following: patients with locally advanced inoperable or MRCC who are starting first-line treatment with sunitinib, with histologically or cytologically confirmed renal cancer clear cell variant or with a clear cell component, and with Karnofsky performance status ≥70%. The primary objective is to assess the median duration of sunitinib treatment (DOT) in each group. The key secondary objectives are progression-free survival, overall survival, time to randomization, objective response rate, safety, sunitinib dose intensity, health-related quality of life, and the description of main drivers triggering randomization. We hypothesized that experimental schedule 2/1 would result in an improvement in median DOT from 6 to 8.5 months. It was estimated that 112 patients would be needed in each arm during 24 months. In order to take into account the possibility of treatment discontinuation before randomization, 248 patients are necessary. DISCUSSION: The SURF trial is asking a pragmatic question adapted to the current practice on what is the best way to adapt sunitinib when treatment-related adverse events occur. The results of the SURF trial will bring high-value data to support the use of an alternative schedule in sunitinib treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02689167 . Registered on 26 February 2016.

Factors Influencing Overall Survival for Patients With Metastatic Clear-Cell Renal-Cell Carcinoma in Daily Practice.

PURPOSE: To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies. PATIENTS AND METHODS: Two hundred twenty-four consecutive patients with histologically confirmed mccRCC who received targeted therapy on first-line treatment between January 2007 and March 2015 were included. The primary end point was OS for metastatic first-line or second-line treatment. An analysis of prognostic factors of long survival was performed using a 2-step approach: univariate, then multivariate analysis. RESULTS: Median OS [95% confidence interval] was 19.4 months [16.1-24.9]. Three prognostic factors were identified in first-line treatment: Memorial Sloan Kettering Cancer Center (MSKCC) favorable and intermediate risks (hazard ratio [95% confidence interval] = 0.362 [0.207-0.630] and 0.561 [0.393-0.801], respectively, P = 4.10-4), metastasectomy (0.667 [0.468-0.951], P = .03), and lack of lymph node metastasis (0.715 [0.513-0.994], P = .049). In second-line treatment, median OS [95% confidence interval] was 11.0 months [8.9-14.4] for 167 patients. Three different prognostic factors predicted long survival: toxicity for first-line treatment discontinuation (HR [95% confidence interval] = 0.298 [0.180-0.493], P < 10-4), duration of disease control in first-line therapy (0.961 [0.942-0.979], P = 2.10-4), and MSKCC favorable and intermediate risks (0.461 [0.252-0.843] and 0.936 [0.607-1.443], respectively, P = .02). CONCLUSION: These real-life data confirm the positive impact of targeted therapy in the mccRCC setting. Moreover, it emphasizes the importance of considering many factors in order to better estimate prognosis in patient pretreated with systemic therapy.

Angiosarcoma: A Case Report of Gingival Disease with Both Palatine Tonsils Localization.

Angiosarcomas are one of the rarest subtypes of sarcomas; those are malignant vascular tumors arising from vascular endothelial cells. Occurrence of intra-oral angiosarcoma is extremely rare (0.0077% of all cancers in Europe). We present here, to our knowledge, the first case of a 83-year-old man with gingival and both palatine tonsils localization of a grade-two angiosarcoma discovered after a two months history of a painful lesion followed by hematoma and spontaneous bleeding. Chemotherapy with paclitaxel and hemostatic radiotherapy were inefficient and he died seven months after the first symptoms. It is essential to use the vascular markers, such as CD34, CD31, ERG and FLI1, for a correct histological diagnosis, which remains difficult because it displays a wide range of morphological appearances and multiple patterns may be present in the same tumor. The main prognostic factors are chronic pre-existing lymphedema and tumor size greater than five centimeters. Malignancy grade and stage classification should be provided in all cases in which this is feasible because of predictive meaning. When possible, wide surgical resection with negative margins remains the cornerstone for the treatment of localized angiosarcomas, but despite the improvement of surgical techniques the prognosis is poor with more than half of patients died within the first year. Adjuvant radiotherapy is the standard treatment of high-grade (two and three), deep lesions, regardless of size, because it improved the local recurrence-free survival. For advanced disease, if possible, metastasectomy should be considered. The first-line chemotherapy with doxorubicin or paclitaxel should be discussed compared to best supportive care according to patient comorbidities and preference.

Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.

After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials.

[Prevalence and management of pain in patients with metastatic cancer in Franche-Comté]. / Prévalence et prise en charge de la douleur chez les patients présentant un cancer métastatique en Franche-Comté.

INTRODUCTION: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain. METHODS: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included. RESULTS: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life. CONCLUSION: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate.

Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity.

The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, a high rate of Eomes(+)CD8(+) T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift toward decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice confirmed the deleterious effect of rapalogs-induced Tregs via a mechanism involving the inhibition of antitumor T-cell immunity. Consequently, the combination of temsirolimus plus CCR4 antagonist, a receptor highly expressed on rapalogs-exposed Tregs, was more effective than monotherapy. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T-cell immunity on the clinical effectiveness of rapalogs and prompt their association with immunotherapies. Cancer Res; 76(14); 4100-12. ©2016 AACR.

Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study.

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m2 intravenous infusion on days 1-3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months [95% confidence interval (CI): 1.9-4.2] and the median overall survival (OS) was 8.1 months (95% CI: 4.06-12.36). The main grade 3-4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocytopenia (22.2%), whereas the most common non-hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treatment-related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospective investigation to confirm its efficacy.

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma.

INTRODUCTION: The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. PATIENTS AND METHODS: All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. RESULTS: For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13-22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22-0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31-0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22-0.82], P=0.002). Median OS was 21 months [14-29 months] for patients who received at least one targeted therapy compared with 12 months [7-15 months] for patients who were treated only by immunotherapy agents (P=0.003). CONCLUSION: Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications.

Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.

PURPOSE: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol. EXPERIMENTAL DESIGN: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months. RESULTS: Eight dose levels (40-8,000 µg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 µg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 µg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 µg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days. CONCLUSION: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned.

Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer.

PURPOSE: We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. RESULTS: Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%). CONCLUSION: The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

[Immunotherapy: an emerging strategies against prostate castration resistant cancer]. / L'immunothérapie : une nouvelle approche dans la prise en charge du cancer de prostate résistant à la castration.

Castration resistant prostate cancer occurs when patients experience disease progression despite appropriate hormonal manipulations. In these patients, chemotherapy remains standard treatment. Preclinical and clinical data have demonstrated the potential utility of an immunotherapy-based approach for the treatment of prostate cancer (PC). The phase III trial (IMPACT) has recently reported an advantage for Sipuleucel-T over placebo, with an overall survival 4.1 months superior to placebo. Sipuleucel-T is also the first FDA-approved immunotherapy for prostate cancer. These promising results need to be confirmed with other large studies and within previous step of PC. Neoplasic cells can escape immune responses by multiple mechanisms. A better knowledge of these mechanisms is of major concern for the future development of new immunotherapies approach.

[Follow-up in patients with early breast cancer]. / La surveillance du cancer du sein non métastasé

Breast cancer incidence remains the highest among gynaecologic neoplasms. Once they have achieved their treatments, patients should undergo careful follow-up. It aims at detecting early local recurrence or controlateral breast cancer. Based on large cohorts, clinical and radiological follow-up procedures come from guidelines realised by scientific organisations. We evaluated our regional practices in Franche-Comté and compared them to current guidelines. Patients with early breast cancer positive for hormonal receptors filled a questionnaire concerning their follow-up. It included patients treated from 1999 to 2005. When frequency of consultation is evaluated, only half of the patients undergo what is recommended. Whereas mammography and non-validated complementary exams are more regularly realised. Patients consulting more one practician have a better compliance. Our study underlines significant disparities among patients follow-up. Better interactions between physicians and a greater implication of patients in their follow-up would increase its quality.

Safety profile of new anticancer drugs.

IMPORTANCE OF THE FIELD: The development of targeted anticancer therapies stems from advances in molecular biology. New agents range from antibodies that form complexes with antigens on the surface of the cancer cell to small molecules that have been engineered to block key enzymatic reactions. The interaction of the antibody or drug with its target inhibits key pathways involved in cell proliferation or metastasis, or activates pathways leading to cell death. Such pathways constitute ideal pharmacological targets. Clinical benefits from these novel therapeutic strategies are striking for patients with metastatic diseases. AREAS COVERED: This review analyses the main toxicities among most common targeted therapies that have been approved by the FDA or European Medicines Agency for their clinical utilisation in solid tumours treatment. WHAT THE READER WILL GAIN: Here, the main toxicity and safety data among new anticancer targeted therapies are described. Data are organised through the pathways targeted by the drugs. TAKE HOME MESSAGE: The emergence of new targeted anticancer therapies promises more efficient and less toxic therapies. Generally, they are well tolerated, toxicities are commonly mild to moderate and can be handled rapidly. However, if most of these adverse events are manageable, life threatening and fatal complications can still occur.

Ixabepilone, a novel epothilone analog in the treatment of breast cancer.

BACKGROUND: Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing cell death. Ixabepilone (BMS-247550, Ixempra) is an epothilone analog that optimizes the properties naturally observed with epothilone B. OBJECTIVE: To provide an overview of the results achieved by ixabepilone in metastatic breast cancer. METHODS: A PubMed search was performed to provide an extensive review of all published data on ixabepilone, in addition to all data reported from international congresses, from 2003 to 2007. RESULTS/CONCLUSION: There is a clear need for new agents active against resistant metastatic breast cancer and ixabepilone might be a welcome new compound in this situation.

Anticancer therapy in patients with porphyrias: evidence today.

BACKGROUND: Porphyrias are rare diseases, and for these patients every administration of drugs may induce an acute attack of porphyria. The list of safe compounds allowed in these patients is available for clinicians from specific websites cited in the text. OBJECTIVES: However, data concerning anticancer therapy in patients with such diseases remain poor. Therefore any publications can help clinicians to deal with this very specific group of patients. METHODS: In our institution, three patients received docetaxel and hematologic growth factors (erythropoietin and GCSF) without unexpected toxicities. Aromatase inhibitors (anstrozole and letrozole) were also given in one patient without any related problem. CONCLUSION: The present observation adds some useful data for the possible treatment of cancer in patients with porphyria.

[Pemetrexed development in oncology]. / Perspectives de développement du pemetrexed en oncologie.

The pemetrexed disodium (Alimta), LY231514) is the first antifolate able to inhibit at the same time the synthesis of purins and pyrimidins. Many therapeutic tests were carried out in clinical situations where the methotrexate and the fluorouracil had been the proof of their effectiveness. It then showed an interesting activity in a great number of tumours but with very different profiles of tolerance according to the studies and pathologies. The explanation will come in 2001 by the description from the relation between the vitamin deficiencies among treated patients and occurred from toxicities. The two randomized studies carried out in the malignant pleural mesothelioma and the non small cell lung cancer made it possible to establish its utility and to record the pemetrexed in these clinical situations. Others axes of development remain possible, but the results are stanby or to confirm as in squamous-cell cancer in the head and neck and breast, digestive or urinary tracts cancer. In all the cases, the optimization of the pemetrexed in terms of amount/methods of administration and associations possible because of its profile of tolerance makes of it a molecule of chemotherapy with a future.