levoleucovorin and Endometrial-Neoplasms

Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs.. Induction treatment was free of life-threatening complications. Nine consecutive patients, 3 under second- and 6 under multi-line treatment, had 9 objective responses and 8 produced long clinical benefits, 2 of which were complete responses. Seven responses created opportunities for personalized added treatment and research. Absolute median survival was 21.5 months for the 8 patients with platinum-resistant tumors. One patient was unable to tolerate a first standard adjuvant dose of paclitaxel. After rapid peritoneal progression of disease, treatment has produced 52+ months of unmaintained complete remission.. Bev, in the combination that was used in this study, meets response, survival, and toxicity criteria for further testing against second- or multi-line chemotherapy-resistant tumors and also when a standard treatment is not safe.

Topics: Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bile Duct Neoplasms; Camptothecin; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Docetaxel; Endometrial Neoplasms; Female; Fluorouracil; Gemcitabine; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Taxoids

MMR-D pancreatic cancer have been reported to respond to checkpoint inhibitor therapy. Here, we report the first case of acquired resistance to immunotherapy in MMR-D pancreatic cancer.. A 45-year-old woman with unresectable MMR-D pancreatic cancer was initially treated with FOLFIRINOX, FOLFIRI, and stereotactic body radiation with stable disease burden. After 3 months, imaging showed progression of disease with an increase in CA19-9. She was subsequently enrolled in a clinical trial of an anti-PD-L1 antibody in combination with an IDO1 inhibitor. She demonstrated a partial response to therapy by RECIST 1.1 criteria with declining tumor markers. Twenty-two months after beginning immunotherapy, imaging revealed an increasing left ovarian cystic mass. There were no other sites of progressive disease. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy, appendectomy, omentectomy and pelvic lymphadenopathy. Pathology was consistent with a metastasis from the pancreas involving the endometrium and left ovary. Thereafter, the patient continued with PD-1 blockade therapy off protocol with no further progressive disease. Immune profiling showed high levels of CD8+ T cells and PD-1 positive immune cells infiltrating the tumor, with a moderate level of PD-L1 expression in both the immune cells and the tumor cells. Next generation sequencing found only the KRAS G12D and RNF43 G659Vfs*41 mutations were retained from the pre-treatment tumor in the treatment-resistant tumor.. This is the first report describing acquired resistance to immunotherapy in MMR-D pancreatic cancer with accompanying genomic and immune profiling. This case of oligoprogression in the setting of immunotherapy demonstrates the feasibility of localized treatment followed by continuation of immunotherapy to sustain ongoing response.

Topics: Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Camptothecin; Drug Resistance, Neoplasm; Endometrial Neoplasms; Female; Fluorouracil; Humans; Immunotherapy; Indoleamine-Pyrrole 2,3,-Dioxygenase; Irinotecan; Leucovorin; Middle Aged; Ovarian Neoplasms; Oxaliplatin; Pancreatic Neoplasms

Women suffering from recurrent platinum-resistant ovarian carcinoma go through several lines of chemotherapy, but eventually fail all conventional chemotherapy options. After failing multiple other regimens, we offer patients fluorouracil (5-FU) in a weekly regimen with leucovorin. For those women who failed to react to multiple lines of treatment, 5-FU has been shown to be a reasonable option with reported response rates of 10% to 33%. We report our experience with 5-FU+leucovorin in this patient population.. This is a retrospective chart review of women treated for recurrent ovarian carcinoma between January 2003 and December 2009. Women with recurrent ovarian carcinoma who had been treated with at least 3 previous chemotherapy regimens and had received 5-FU were eligible for the study. 5-FU and leuocovorin are given at 600 mg/m weekly for 6 weeks of an 8-week cycle. Patient charts were reviewed for demographics and disease history relevant to the administration of 5-FU. Response was assessed clinically and by CA125 levels.. Fifty-three patients matching inclusion criteria received 5-FU during the study period. Twenty-five percent of patients achieved a partial response and 17% stable disease for an overall response rate of 42%. A median of 4 weekly doses was administered (range, 1 to 26). The median survival of the whole cohort was 10 weeks after the last dose of 5-FU was administered.. In this population of heavily pretreated patients, a significant response to 5-FU can be achieved. Unfortunately, the response is short lived and mostly partial.

Topics: Adenocarcinoma, Mucinous; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Papillary; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Retrospective Studies; Survival Rate