Docetaxel in the Management of Advanced Pancreatic Cancer

The poor outcome of pancreatic cancer with conventional treatment options emphasizes the need for continued research. The benefits of gemcitabine in improving quality of life and survival have been established in patients with advanced pancreatic cancer. Randomized clinical trials studying the addition of a second drug to gemcitabine, either a classic cytotoxic (5-fluorouracil, cisplatin, irinotecan, pemetrexed, oxaliplatin, or exatecan) or targeted agents (ie, the farnesyl transferase inhibitor R115777 or the metalloproteinase inhibitor marimastat) have not resulted in improvement in survival compared with gemcitabine alone. Although limited activity of docetaxel in patients with pancreatic adenocarcinoma has been reported in single-agent studies, attractive efficacy results have been documented with docetaxel in combination with other chemotherapeutic agents for the management of advanced pancreatic cancer. Phase I and II trials of docetaxel in combination with gemcitabine, irinotecan, 5-fluorouracil, or thalidomide, as well as trials of docetaxel and radiotherapy, suggest that docetaxel combinations in pancreatic cancer should be further studied in randomized trials

Impact of Hispanic ethnicity on the clinical presentation and survival of esophageal and gastric cancer in south Florida.

125 Background: Race and ethnicity are associated with differences in survival among patients with esophageal and gastric cancer (EGC); outcomes are better in Asian patients but worse for African-Americans compared to Caucasians and Asians. Limited data exist for Hispanics (Hisp) compared to non-Hispanic whites (NHW) or African-Americans (AA). Because of the large Hisp population in South Florida, we compared the clinical presentation and survival of patients with EGC by race and ethnicity. Methods: Using a cross-sectional study design, this IRB-approved analysis of the Florida Cancer Data System database identified all patients diagnosed at the University of Miami and Jackson Memorial Hospital between January 2000 and December 2012 with squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus, and adenocarcinomas of the gastro-esophageal junction (GEJ) or stomach (STO). Demographic, treatment and survival data were extracted from the registry. Survival was analyzed using the Kaplan-Meier method and variables associated with survival were analyzed using a Cox proportional hazards model. Results: Data from 2,170 patients were available; 44% were Hisp, 19% AA and 38% NHW. Compared to NHW's and AA's, Hisp's were more likely to have the following features: male gender, advanced age at cancer diagnosis, esophageal site of malignancy, adenocarcinoma histology, earlier stage at presentation, history of smoking and alcohol use, private insurance, surgical resection and receipt of chemotherapy (p < 0.001 in each case). Hisp were less likely to have STO (p<0.001). In a multivariate model, race and ethnicity were not independently associated with survival but age, stage, surgical resection and chemotherapy administration were all independently associated with survival (p < 0.01 in each case). Country of birth did not influence results among Hispanic patients. Conclusions: Race and ethnicity were not independently associated with survival in this large registry study. However, significant differences in the tumor location, histology and stage of presentation exist, and further studies to elucidate the biological or environmental reasons for these disparities are warranted

Gemcitabine (G) and nab-paclitaxel (nab-P) in patients with refractory advanced pancreatic cancer (PC).

373 Background: There is no standard chemotherapy regimen for PC patients who have progressed on G and fluoropyrimidine-based therapy. Single agent nab-P had limited activity on a second-line phase II trial in PC. Synergistic preclinical studies with G and taxanes have been reported. Nab-P targets stromal cells and leads to improved delivery of chemotherapy to PC cells. The combination of G + nab-P might be an effective approach in pretreated PC. Methods: A retrospective analysis of advanced refractory PC patients treated from Sep 2010 to Aug 2011 with the combination of G + nab-P was performed at the Sylvester Comprehensive Cancer Center. Patients received G 1000mg/m2 and nab-P 100mg/m2 on D1, 8 and 15 of a 28 day cycle. Treatment response was assessed by review of imaging studies using the RECIST criteria, CA19-9 response and symptomatic improvement. The progression-free survival (PFS) and overall survival (OS) were calculated from time of commencement of G + nab-P until documented progression or death respectively. Results: 10 patients were treated with G + nab-P; 60%, 30% and 10% of patients had received 3, 2 and 1 prior chemotherapy regimen. 90% and 80% received prior G or fluoropyrimidine-based regimen respectively. Therapy was discontinued in one patient following only one dose of G + nab-P (Cycle 1, day 1) due to grade 2 thrombocytopenia. The remaining 9 patients received a median of 4 cycles. Two (22.2%) patients had confirmed PR, 3(33.3%) patients had confirmed stable disease while 4 (44.4%) patients progressed on therapy. The median PFS was 13.7 weeks. The median PFS was 20 weeks in patients with PR or SD and 9.9 weeks in patients with PD. Recurrent malignant ascitis resolved in a patient with peritoneal carcinomatosis. Treatment was well tolerated; grade 3-4 hematologic toxicity included anemia, thrombocytopenia and neutropenia in 2, 1 and 2 patients respectively. 70% of patients required G-CSF support. Non hematologic Grade 3-4 toxicities included fatigue, peripheral neuropathy; nausea and vomiting in 3, 2 and 1 patient respectively. Conclusions: G + nab-P resulted in clinical benefit in half of this group of advanced PC patients who had previously progressed on G and fluoropyrimidine-based regimens

A retrospective cohort study to determine the prognostic factors in metastatic colorectal cancer (mCRC) patients (pts) undergoing lung metastatectomy.

565 Background: Resection of liver metastases is now accepted as a potentially curative strategy in some pts with mCRC. Resection of lung metastases (LMs) may also be beneficial but this is not well established. We hypothesized that resection of LMs may lead to prolonged survival in highly selected pts with mCRC. Methods: In this IRB-approved retrospective cohort study, cases were defined as mCRC pts with LMs as their only site of disease who underwent metastatectomy. Controls consisted of mCRC pts who had LMs but did not undergo resection. Charts were reviewed for clinical characteristics; survival data was obtained from the institutional tumor registry. The primary endpoint was overall survival (OS) in the cases versus controls. The secondary endpoint was to determine prognostic factors associated with better survival. Results: We included 26 consecutive cases of mCRC undergoing resection of LMs and randomly selected 26 controls. All pts in the both groups were treated with contemporary chemotherapy, as well as bevacizumab and anti-EGFR monoclonals when appropriate. The median OS from the time of diagnosis with LMs was 29.8 months (95% CI 22.9-36.6) in the control group versus 56.6 months (95% CI 47.3-65.8) for the cases who underwent resection (log rank p=0.04). A number of baseline factors were significantly different between the cases and controls. The control group contained more pts with poorly differentiated tumors (p=0.016); had more pts with synchronous versus metachronous presentation of LM's (p=0.001); had more pts with multiple vs solitary LM's (p<0.001); and had more pts with bilateral vs unilateral LMs (p<0.001). The interval from initial diagnosis to the onset of LMs was significantly longer in the resection group vs controls (22.9 vs 2.9 months, p<0.001). Conclusions: In this retrospective study, pts with mCRC to the lung who were referred for resection were more likely to have well differentiated, solitary, unilateral tumors, with a long interval between the original diagnosis and the onset of LMs. Pts selected using these criteria may have a significant survival benefit from surgical resection of their LMs

A retrospective study of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (GC)

138 Background: Perioperative chemotherapy (chemo) with ECF (epirubicin/cisplatin/5-fluorouracil) plus surgery improved survival over surgery alone in GC in the MAGIC trial. Herein we report our experience using DCF in the perioperative setting in patients (pts) with locally advanced GC. Methods: We conducted a retrospective IRB-approved study of pts with potentially resectable locally advanced GC who were treated with DCF with neoadjuvant intent. Pts received 3 cycles of preoperative (pre-op) DCF every 3 weeks, followed by surgery, then 3 cycles of postoperative (post-op) DCF. Patients with a poor pathologic response could be changed to radiation (RT) or an alternate chemo regimen postop. Results: A total of 41 pts were identified, 24 with gastric and 17 with GEJ adenocarcinoma. All pts received at least 1 cycle of DCF and 78% received at least 3 cycles pre-op. Five pts progressed during neoadjuvant DCF, 4 were unresectable by CT after neoadjuvant DCF and 2 were lost to follow-up. The remaining 30 pts had surgery with curative intent. Post-op, 2 pts were lost to follow-up, 12 received DCF (with 6 of these also receiving RT), 11 received a different chemo regimen due to a poor response to neoadjuvant DCF (including 6 pts who also received RT). Two pts received post-op RT only. The median PFS was 16.8 months (95% CI 7.7 - 25.9) and the median OS was 26.9 months (95% CI 18.7–35.1). The PFS was longer for pts who had a radiological or pathological response to neoadjuvant DCF (log rank p = 0.005 and 0.02 respectively) and for pts who received DCF post-op (log rank p = 0.005). Among pts who did not receive DCF post-op, there was no survival difference between the pts who were switched to an alternative chemo or chemoRT regimen post-op compared to those who received no further therapy. The most common chemo-related adverse events were anemia (27% grade 3 or 4), nausea/vomiting (17% G3 or 4), and febrile neutropenia (12%). Conclusions: The DCF regimen is well tolerated in locally advanced GC. Patients who do not have a good response (either radiologic or pathologic) to pre-op DCF appear to have a poor prognosis regardless of the post-op treatment given

Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma

Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting

Does delay of adjuvant chemotherapy impact survival in patients with resected stage II and III colon adenocarcinoma?

It is unclear whether delays in commencing adjuvant chemotherapy after surgical resection of colon adenocarcinoma adversely impact survival. Patients with stage II-III colon adenocarcinoma who received adjuvant chemotherapy at 2 centers were identified through the institutional tumor registry. Time to adjuvant chemotherapy, overall survival (OS), and relapse-free survival (RFS) were calculated from the day of surgery. Patients were dichotomized into early (time to adjuvant chemotherapy ≤ 60 days) and late treatment (time to adjuvant chemotherapy >60 days) groups. OS and RFS were compared using log-rank test and multivariate analysis by the Cox proportional hazards model. Of 186 patients included in the study, 49 (26%) had received adjuvant chemotherapy >60 days after surgical resection. Thirty percent of the delays were system related (eg, late referrals, insurance authorizations). Time to adjuvant chemotherapy >60 days was associated with significantly worse OS in both univariate analysis and a Cox proportional hazards model (hazard ratio, 2.17; 95% confidence interval, 1.08-4.36). Although difference in RFS between the 2 groups favored time to adjuvant chemotherapy <60, this did not reach statistical significance. Adjuvant chemotherapy delay >60 days after surgical resection of colon cancer is associated with worse OS