Early treatment modifications improve chemotherapy adherence in ovarian cancer patients ≥70 years.

OBJECTIVE: Elderly ovarian cancer patients are underrepresented in clinical trials and disadvantaged with regard to therapeutic standards compared to other age groups. We explored the specific performance of a subset of patients aged ≥70 years in a large meta-data set of 3 phase III trials. METHODS: 3333 patients with advanced ovarian cancer recruited into 3 clinical phase III trials of the AGO & GINECO study groups were retrospectively analysed for age-specific prognostic and toxicity parameters. RESULTS: Only 10% (359/3333) of the patients were aged ≥70 years. This subgroup presented with impaired performance statuses (ECOG 2 14.8 vs 10.1%) and higher FIGO-stages (FIGO IIIC-IV 78.5 vs 73.6%) compared to younger patients. Complete operative tumor resection was achieved less frequently (postoperative tumor burden >10 mm 46.7 vs 33.9%) and elderly received less cycles of platinum/taxane-based chemotherapies (>4 cycles 81.9 vs 90.7%). FIGO-stage, histology, postoperative tumor burden and number of chemotherapy cycles were independent prognostic factors in elderly patients. Elderly patients with ≤4 cycles of chemotherapy showed a median OS of 18.4 months compared to 30.9 months in elderly with 5-6 cycles (p < 0.001). This effect was accentuated in elderly patients after complete tumor resection (cumulative survival benefit of 33.8 months). Analyses of chemotherapeutic delivery revealed that elderly patients with at least one cycle delay had higher chances to complete >4 cycles of chemotherapy. CONCLUSIONS: Protocol defined treatment modifications might support completion of >4 cycles of standard chemotherapy in fit elderly OC patients.

Antifreeze proteins in the primary urine of larvae of the beetle Dendroides canadensis.

To avoid freezing while overwintering beneath the bark of fallen trees, Dendroides canadensis (Coleoptera: Pyrochroidae) larvae produce a family of antifreeze proteins (DAFPs) that are transcribed in specific tissues and have specific compartmental fates. DAFPs and associated thermal hysteresis activity (THA) have been shown previously in hemolymph and midgut fluid, but the presence of DAFPs has not been explored in primary urine, a potentially important site that can contain endogenous ice-nucleating compounds that could induce freezing. A maximum mean THA of 2.65±0.33°C was observed in primary urine of winter-collected D. canadensis larvae. THA in primary urine increased significantly through autumn, peaked in the winter and decreased through spring to levels of 0.2-0.3°C in summer, in a pattern similar to that of hemolymph and midgut fluid. THA was also found in hindgut fluid and excreted rectal fluid, suggesting that these larvae not only concentrate AFPs in the hindgut, but also excrete AFPs from the rectal cavity. Based on dafp transcripts isolated from Malpighian tubule epithelia, cDNAs were cloned and sequenced, identifying the presence of transcripts encoding 24 DAFP isoforms. Six of these Malpighian tubule DAFPs were known previously, but 18 are new. We also provide functional evidence that DAFPs can inhibit ice nucleators present in insect primary urine. This is potentially critical because D. canadensis larvae die if frozen, and therefore ice formation in any body fluid, including the urine, would be lethal.