Susan Talbot

Multiepitope CD8+ T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting

The cancer-testis antigen NY-ESO-1 is one of the most promising candidates for generic vaccination of cancer patients. Here we analyzed the CD8(+) T cell response to a NY-ESO-1 peptide vaccine composed of the two previously defined peptides 157-165 and 157-167, administered with GM-CSF as a systemic adjuvant. The NY-ESO-1 peptide vaccine elicited a CD8(+) T cell response directed against multiple distinct epitopes in the 157-167 region, as revealed by using A2/peptide multimers incorporating overlapping A2 binding peptides in this region. However, only a minor fraction of the elicited CD8(+) T cells, namely those recognizing the peptide 157-165 with sufficiently high functional avidity, recognized the naturally processed target on NY-ESO-1(+) tumor cells. In contrast, the majority of peptide 157-165-specific CD8(+) T cells exhibited lower functional avidity and no tumor reactivity. In addition, vaccine-elicited CD8(+) T cells specific for other overlapping epitopes in the 157-167 region failed to significantly recognize NY-ESO-1-expressing tumor targets. Thus, because of the complexity of the CD8(+) T cell repertoire that can be elicited by vaccination with synthetic peptides, a precise definition of the targeted epitope, and hence, of the corresponding peptide to be used as immunogen, is required to ensure a precise tumor targeting.

A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma

The objective of this study was to assess the efficacy and toxicity of the imidazotetrazine derivative temozolomide for patients with unresectable or metastatic soft tissue sarcoma.

Combined Resection, Intraperitoneal Chemotherapy, and Whole Abdominal Radiation for the Treatment of Malignant Peritoneal Mesothelioma

Objective:We report a single-institution Phase I or II trial of surgical debulking, intraperitoneal chemotherapy, and immunotherapy followed by whole abdominal radiotherapy in patients with malignant peritoneal mesothelioma. Methods:Between 1997 and 2000, 27 patients with malignant peritoneal mesothelioma were enrolled: 23 with epithelial subtype and 4 with sarcomatoid or mixed subtype. The treatment regimen consisted of surgical debulking followed by 4 intraperitoneal courses of cisplatin alternating with 4 courses of doxorubicin, 4 doses of intraperitoneal gamma interferon, a second laparotomy with resection of residual disease plus intraoperative intraperitoneal mitomycin and cisplatin heated to 41°C, and finally whole abdominal radiotherapy. Results:The median overall survival was 70 months with a 3-year survival of 67% (95% confidence interval, 46%–81%). Fourteen patients have died of their disease with a median time to death of 17 months (range, 0.4–71 months) after consenting to treatment. Seven patients are alive without evidence of disease with a median follow-up of 90 months (range, 71–110 months), and 6 are alive with disease with a median follow-up of 86 months (range, 70–106 months). The regimen was well tolerated. There were no patients with Grade III or IV hematological toxicities, 2 patients with Grade III ototoxicity, and 3 patients with Grade III gastrointestinal toxicity. Conclusion:Based on the results of this study, intensive multimodality therapy appears feasible and effective in this group of patients.

Combined Fludarabine and Rituximab for Low Grade Lymphoma and Chronic Lymphocytic Leukemia

As both fludarabine and rituximab are active against indolent lymphoproliferative disorders, we have studied the combination of fludarabine and rituximab in patients with low-grade lymphoma and chronic lymphocytic leukemia (CLL) in phase I/II fashion. Of 33 patients enrolled, 21(63.6%) had low-grade lymphoma and 12 (36.4%) had CLL. They received fludarabine 30 mg/m 2 on days 1-4 and rituximab 125, 250 or 375 mg/m 2 on day 5 at intervals of 28 days to a maximum of 8 cycles. Three patients were removed from the study because of rituximab-associated anaphylaxis and four because of prolonged hematopoietic toxicity. Toxicity and responsiveness did not differ at the different dose levels of rituximab. For 29 evaluable patients, responses were seen in 82.8% and complete responses in 34.5%. Of 7 responding patients not referred for stem cell transplantation, 6 remain in complete remission at a median follow-up of 16 months (range 4-30 months). Of 13 previously untreated patients, all responded and 46.2% had a complete response. Of 16 previously treated patients, 68.5% responded and 25% had a complete response. The combination of fludarabine and rituximab has major activity and acceptable toxicity in patients with low-grade lymphoma and CLL.

A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma

The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P‐glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over‐express P‐glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC).

Integration of palliative care services into standard oncology practice at diagnosis of metastatic lung cancer at VA New York Harbor Healthcare System.

165 Background: The 2012 ASCO provisional clinical opinion addressed the integration of palliative care into standard oncology practice at the time a person is diagnosed with metastatic or advanced cancer. The inclusion of Palliative Care among the National Quality Forum (NQF) framework represented a major advance in palliative care. NQF metrics include chemotherapy administered in the last 14 days of life, hospice less than 3 days before death, ICU or hospital admission, more than one Emergency Room visit in the last 30 days, and death in hospital. Although the use of hospice and other palliative care services has increased, many are enrolled in hospice less than 3 weeks before death. By improving quality of life, cost, and survival in patients with metastatic cancer, palliative care has increasing relevance for the care of patients with cancer. METHODS Retrospective chart review study of lung cancer patients diagnosed at VA from 2010-2013. INCLUSION CRITERIA > 18 years of age with new diagnosis of metastatic lung cancer. EXCLUSION CRITERIA < 18 years of age, Stage I-III lung cancer. RESULTS Total of 125 patients were diagnosed with Stage IV lung cancer. The mean time from diagnosis to death was only 185 days (6.1 months). The VA NYHHS patients were more likely to visit the ED, be admitted to the hospital and ICU in the last 30 days of life, and subsequently die in the hospital. CONCLUSIONS Several confounders were identified, including climate related closure of facilities (2012 Sandy storm), lack of social support, low ICU admission criteria, burial benefits for patients dying in a VA, and delay in transition to Hospice. Currently 392 patients with stage IV solid tumors diagnosed 2010-2014 are being studied. [Table: see text].