PurposeThe miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC).MethodsAn open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death.ResultsFifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%.ConclusionsThe combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785

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Thank you very much for the opportunity to reply to the letter to the editor by Dr. Dhruva Rao et al. We would like to thank them for their interesting comments.In our study, the initial port was placed through the colostomy site in 21 of 27 patients (77.8%) with pneumoperitoneum established through the Hasson cannula at the colostomy site. Two additional ports were then inserted under direct vision to allow adhesiolysis. Subsequently, some of the surgeons moved the camera location to a newly-inserted midline port. We agree that it may be both possible and safe to use the stoma site to insert a midline camera port first by palpation of the wall, especially in thin patients without massive adhesions to the abdominal wall.Regarding their second comment, in our series there were no parastomal hernias at the time of the reversal. However, adhesiolysis under laparoscopic vision can facilitate dissection around the stoma and colostomy mobilization. Likewise, mobilization of the left colon even without splenic flexure in patients with paracolostomy hernia may be difficult through the colostomy site and requires additional intracorporeal dissection to ensure a safe tension-free anastomosis.Once again, we thank Dr. Rao and his colleagues for their interesting comments.