Two cases of avulsion fracture of the anterior inferior iliac spine are reported. One was a missed diagnosis that resulted in exostosis formation needing excision. The second case was an adolescent with significant displacement of the fragment and a primary open reduction and internal fixation was done. A high index of suspicion is necessary to diagnose this relatively rare injury and surgery has a role in carefully selected cases.Résumé Deux cas d'avulsion-fracture de l'épine iliaque antéro-inférieure sont rapportés. Dans un cas ou le diagnostic n'a pas été fait l'évolution s'est fait vers une ossification qui a nécessité une exérèse. Le deuxième cas était un adolescent avec une fracture à grand déplace-ment et une réduction ouverte et fixation interne a été faite. Un haut index de soupçon est nécessaire pour diagnostiquer cette lésion relativement rare et la chirurgie a un rôle dans certains cas sélectionnés.

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Preventing chemotherapy-induced thrombocytopenia could avoid chemotherapy dose reductions and delays. The safety and maximum tolerated dose of eltrombopag, an oral thrombopoietin receptor agonist, with gemcitabine-based therapy was evaluated. Patients with advanced solid tumors and platelets ≤300 × 109/L receiving gemcitabine plus cisplatin or carboplatin (Group A) or gemcitabine monotherapy (Group B) were randomized 3:1 to receive eltrombopag or placebo at a starting dose of 100 mg daily administered on days −5 to −1 and days 2–6 starting from cycle 2 of treatment. Nineteen patients (Group A, n = 9; Group B, n = 10) received eltrombopag 100 mg and seven (Group A, n = 3; Group B, n = 4) received matching placebo. Nine eltrombopag patients in Group A and eight in Group B had 38 and 54 occurrences of platelet counts ≥400 × 109/L, respectively. Mean platelet nadirs across cycles 2–6 were 115 × 109/L and 143 × 109/L for eltrombopag-treated patients versus 53 × 109/L and 103 × 109/L for placebo-treated patients in Groups A and B, respectively. No dose-limiting toxicities were reported for eltrombopag; however, due to several occurrences of thrombocytosis, a decision was made not to dose-escalate eltrombopag to >100 mg daily. In Groups A and B, 14% of eltrombopag versus 50% of placebo patients required chemotherapy dose reductions and/or delays for any reason across cycles 3–6. Eltrombopag 100 mg once daily administered 5 days before and after day 1 of chemotherapy was well tolerated with an acceptable safety profile, and will be further tested in a phase II trial. Fewer patients receiving eltrombopag required chemotherapy dose delays and/or reductions compared with those receiving placebo.

Background: In HER2 over-expressing breast cancer cells, the HER2 protein can be cleaved by a metalloproteinase, ADAM10. While the extracellular domain (ECD) of HER2 is released into the serum, the truncated HER2 receptor fragment, termed p95, remains in the tumor cell membrane as a constitutively active receptor tyrosine kinase. Previous studies have shown that the presence of p95 in tumor cells is associated with poor clinical outcomes in patients with metastatic HER2 positive breast cancer and it was recently shown that patients with p95+ HER2 positive breast cancer are resistant to trastuzumab-based therapy. Therefore, inhibition of HER2 cleavage by the ADAM10/ADAM17 inhibitor, INCB7839, which reduces the formation of soluble HER2 ECD as well as p95 levels in the tumor, may enhance the clinical efficacy of trastuzumab in HER2+ breast cancer patients. Materials and Methods: This study is a single arm modified dose escalation open label trial of INCB7839 + trastuzumab in women with HER2+ metastatic breast cancer, naïve to chemotherapy. Three doses of INCB7839 were studied (100 mg, 200 mg, 300 mg BID) with 6 patients/cohort and an expansion arm at the 300mg BID dose. Herceptin was administered on a Q3 week schedule. Pharmacokinetics, plasma HER2 ECD levels and p95 expression in tumor tissue were assessed in addition to clinical response and safety. Results: 39 patients have been enrolled in the study and assessment of HER2 ECD levels, p95 status and best clinical response completed on 30 patients. INCB7839 administration results in a dose-dependent reduction in the elevated levels of circulating HER2 ECD with a mean of ∼80% inhibition achieved at the highest dose tested (300 mg BID). At the 300mg BID dose, the current overall response rate is 40% (6/15 evaluable patients) with a higher response rate (6/11 or 55%) observed in patients with average plasma concentrations of INCB7839 above the IC50 for reduction of ECD levels, 320nM. Importantly, INCB7839 increases the clinical response rate in p95+ patients, with equivalent responses observed in the p95+ and p95- patients treated with INCB7839 + trastuzumab. The combination has been generally safe and well tolerated. Discussion: Proteolytic cleavage of the HER2 receptor by ADAM proteases results in the formation of a cytoplasmic fragment (p95) that possesses constitutive kinase activity with the release of ECD. Importantly, elevated levels of ECD and/or p95 have been associated with poor prognosis and clinical data suggest that p95 affords resistance to trastuzumab. Biomarker and clinical data from this trial demonstrate that INCB7839 can markedly reduce HER2 cleavage in patients with HER2+ breast cancer, and suggests that INCB7839, by inhibiting the HER2 shedding process, can render a subpopulation of HER2+ patients (as defined by the presence of p95) that would be predicted to be trastuzumab resistant clinically responsive to trastuzumab therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5056.

ConclusionsThe most cost-effective treatment for metastatic pancreatic cancer depends on the societal wtp threshold. If the societal wtp threshold were to be relatively high or if drug costs were to be substantially reduced, folfirinox might be cost-effective.