Acute Fatal Liver Toxicity under Erlotinib

We describe the case of a never-smoker who received second-line erlotinib as a treatment for his non-small cell lung cancer. Within one month, acute hepatic failure developed as well as a thrombotic-thrombocytopenic microangiopathy, with fatal outcome. In patients with non-small cell lung cancer, hepatic toxicity of erlotinib is a rare but severe complication; so far three fatal cases have been reported. Patients’ liver function should be assessed before starting erlotinib and special care is recommended if pretreatment bilirubin is elevated

A phase I Study with oral SU5416 in patients with advanced solid tumors: A drug inducing its clearance

Summary: Vascular endothelial growth factor (VEGF) is a potent stimulant of angiogenesis. SU5416, is a small molecule tyrosine kinase inhibitor, and a potent inhibitor of VEGF- mediated Flk-1 receptor signaling. Intravenous agent SU5416 has shown evidence of biological activity against a variety of tumor types. The current intravenous dosing regimen is not optimal for long-term administration, which is needed for optimal efficacy. The aim of this study was to evaluate the safety profile and pharmacokinetics of a Nanocrystal Colloidal DispersionTM (NCD) SU5416 formulation in humans. Patients with advanced and/or metastatic solid organ tumors were included in the trial; various SU5416 regimens were tested for tolerability, safety and were evaluated concerning pharmacokinetics. The results of this study indicate that induction of clearance after oral dosing of NCD SU5416 in humans occurs and is greater than following IV administration. It has been confirmed that SU5416 is a high clearance compound, also as an oral NCD formulation. The NCD formulation was well tolerated, but no effective drug serum levels could be achieved. These data help to understand the ADME (Absorption, Distribution, Metabolism, Excretion) properties of indoline chemical class compounds. The lessons learned should be applied in the development of next generation indoline anti-angiogenic and anti-tumor compound

Dose reduction of epoetin-alpha in the prevention of chemotherapy-induced anaemia

Introduction: Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis. Materials and methods: The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11g/dL. Epoetin-α was administered at a dose level of 3 × 10,000U weekly as soon as Hb descended to < 13g/dL. Dose reductions to 3 × 4,000U and 3 × 2,000U weekly were planned in 4-week intervals if Hb stabilised in the range of 11-13g/dL. Upon ascending to ≥13g/dL, epoetin was discontinued. Iron supplements of 100mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated. Results and discussion: Their median Hb level was 13.7 (10.9-16.2) g/dL at baseline and descended to 11.0 (7.4-13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients. Conclusion: Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantiall

Peptide Receptor Radionuclide Therapy for a Phosphaturic Mesenchymal Tumor.

Tumor-induced osteomalacia is a very rare paraneoplastic syndrome. It can be caused by phosphaturic mesenchymal tumor (PMT), a generally benign tumor that produces fibroblast growth factor 23 (FGF-23), which can cause a severe renal phosphate wasting syndrome. Upon complete surgical removal of the tumor, FGF-23 normalizes and the osteomalacia is cured. In cases in which surgery is not feasible, radiofrequency ablation (RFA) is the treatment of choice. We describe a case with a PMT situated in the sacrum, in close proximity to the sacral plexus. Both surgery and RFA were considered potentially nerve damaging. Since the tumor showed expression of somatostatin receptors, we opted for a peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATOC. However, the therapy did not show the expected success, since the FGF-23 level had even temporarily increased. The patient was then successfully treated with RFA. A partial remission of the tumor was achieved and FGF-23 levels nearly normalized. Despite some severe neurological side effects, the patient showed a remarkable clinical improvement, with no symptoms of osteomalacia within a few weeks

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 500mg/day. Objective responses (ORs) were assessed every 2months 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 110days (95% confidence interval [CI]: 55, 117); median overall survival was 303days (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 ≥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 observe

A Phase II Study of Tg4010 (Mva-Muc1-Il2) in Association with Chemotherapy in Patients with Stage III/IV Non-small Cell Lung Cancer

BackgroundTG4010 is a recombinant viral vector expressing both the tumor-associated antigen MUC1 and Interleukine-2. This vector is based on the modified virus of Ankara, a significantly attenuated strain of vaccinia virus. TG4010 has been designed to induce or amplify a cellular immune response directed against tumor cells expressing MUC1.MethodsA multicenter, randomized phase II study has explored two schedules of the combination of TG4010 with first line chemotherapy in patients with stage IIIB/IV non-small cell lung cancer. In Arm 1, TG4010 was combined upfront with cisplatin (100 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and day 8). In Arm 2, patients were treated with TG4010 monotherapy until disease progression, followed by TG4010 plus the same chemotherapy as in Arm1. Response rate was evaluated according to RECIST. Median time to progression and median overall survival were calculated according to the Kaplan–Meier method.ResultsSixty-five patients were enrolled, 44 in Arm 1 and 21 in Arm 2, in accordance with the two stage Simon design of the statistical plan. In Arm 1, partial response was observed in 13 patients out of 37 evaluable patients (29.5% of the intent to treat population, 35.1% of the evaluable patients). In Arm 2, two patients experienced stable disease for more than 6 months with TG4010 alone (up to 211 days), in the subsequent combination with chemotherapy, one complete and one partial response were observed out of 14 evaluable patients. Arm 2 did not meet the criteria for moving forward to second stage. The median time to progression was 4.8 months for Arm 1. The median overall survival was 12.7 months for Arm 1 and 14.9 for Arm 2. One year survival rate was 53% for Arm 1 and 60% for Arm 2. TG4010 was well tolerated, mild to moderate injection site reactions, flu-like symptoms, and fatigue being the most frequent adverse reactions. A MUC1-specific cellular immune response was observed in lymphocyte samples from all responding patients evaluable for immunology.ConclusionsThe combination of TG4010 with standard chemotherapy in advanced non-small cell lung cancer is feasible and shows encouraging results. A randomized study evaluating the addition of TG4010 to first line chemotherapy in this population is in progress

Prospective, observational practice survey of applied skin care and management of cetuximab-related skin reactions: PROSKIN study.

PURPOSE The study aimed to investigate strategies to prevent and treat cetuximab-induced skin reactions and their perceived effectiveness in patients with metastatic colorectal cancer (mCRC) and recurrent/metastatic squamous cell cancer of the head and neck (SCCHN). METHODS This open-label, prospective observational study was conducted in Switzerland. RESULTS A total of 125 patients were included (n = 91 mCRC, n = 34 SCCHN; mean age 63.3 years; 73.6% males). The frequency of acneiform rash grade ≥ 2 increased from 12.6% at week 2 to 21.7% at week 16. The proportion of patients who reported no skin reaction decreased from 75.6% at week 2 to 43.3% at week 16. The most frequently used skin products at any time of observation were moisturizing (77.6%), lipid-regenerating (56.8%) or urea-containing products (52%), systemic antibiotics (49.6%), and vitamin K1 cream (43.2%). There was no clear effectiveness pattern for all product classes: in given patients, either the product showed no effect at all or a moderate/strong effect, consistently over time. CONCLUSIONS A great variety of low-cost general skin care products were commonly used. According to physician's preference, systemic antibiotics and vitamin K1 cream are an appropriate approach to prevent or treat cetuximab-related skin toxicity

Outcome and Prognostic Factors of COVID-19 Infection in Swiss Cancer Patients: Final Results of SAKK 80/20 (CaSA).

PURPOSE These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. METHODS We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. RESULTS From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus &lt;65 years (OR 3.14, p = 0.003), non-curative versus curative disease (OR 2.42, p = 0.012), ICU admission (OR 4.45, p &lt; 0.001) and oxygen requirement (OR 20.28, p &lt; 0.001) were independently associated with increased mortality. CONCLUSIONS We confirmed high COVID-19 severity and mortality in real-world cancer patients during the first and second wave of the pandemic in a country with a decentralized, high-quality, universal-access health care system. COVID-19-associated mortality was particularly high for those of older age in a non-curative disease setting, requiring oxygen or ICU care

Group-based body psychotherapy improves appreciation of body awareness in post-treatment cancer patients: A non-randomized clinical trial

IntroductionCancer-related impairments often co-occur with bodily disturbances. Body psychotherapy (BPT) can improve bodily wellbeing, yet evidence in cancer survivors is scarce. Hence, we aimed to evaluate whether blended group BPT alleviates bodily disturbances in post-treatment cancer patients.MethodsWe conducted a bi-center study (registered in ClinicalTrials.gov, under No. NCT03707548), applying a pre-post convergent parallel design of weekly group BPT interspersed with smartphone-based ambulatory interventions using a waiting-period comparator. We included patients with completed curatively intended treatment for malignant neoplasms, suffering from bodily disturbances. The primary outcome was body image disturbances. Secondary outcomes were experiencing and appreciating body awareness, mental wellbeing, and health-related quality of life.ResultsForty patients (mean age 51.7 years) attended group BPT. Mixed-effect linear regression models contrasting intervention with the waiting period did not show statistically significant differences regarding the primary outcome [Pre-post difference contrasts: 1.44, 95% confidence interval (CI): −1.51 to 4.93, p = 0.339]. However, patients showed greater improvements in appreciating body awareness, measured by the “Body Mindfulness Questionnaire” (BMQ), from pre- to post-intervention as compared to the waiting period (pre-post difference contrasts: 7.31 95% CI: 4.15–10.47, Bonferroni-Holm corrected q = 0.0002).DiscussionWe found no evidence that blended group BPT was effective in improving body image disturbances in post-treatment cancer patients, but found indications for an increase in body awareness appreciation.Clinical trial registrationClinicalTrials.gov, identifier NCT03707548