Minnie Pearl Cancer Research Network Research Articles

Pasteurella multocida tracheobronchitis in a patient with CLL on rituximab

American Journal of HematologyVolume 85, Issue 2 p. 144-145 CorrespondenceFree Access Pasteurella multocida tracheobronchitis in a patient with CLL on rituximab† Dustin Deming, Dustin Deming Department of Medicine, University of Wisconsin, Madison, WisconsinSearch for more papers by this authorElizabeth Silverman, Elizabeth Silverman Department of Medicine, University of Wisconsin, Madison, Wisconsin Department of Medicine, Hematology-Oncology Section, William S. Middleton Memorial Veterans Hospital, Madison, WisconsinSearch for more papers by this author Dustin Deming, Dustin Deming Department of Medicine, University of Wisconsin, Madison, WisconsinSearch for more papers by this authorElizabeth Silverman, Elizabeth Silverman Department of Medicine, University of Wisconsin, Madison, Wisconsin Department of Medicine, Hematology-Oncology Section, William S. Middleton Memorial Veterans Hospital, Madison, WisconsinSearch for more papers by this author First published: 16 November 2009 https://doi.org/10.1002/ajh.21592 † Conflict of interest: Nothing to report. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Marinella MA. Infections due to Pasteurella multocida. Hosp Physician 1998; 34: 21– 24. 2 Weber DJ,Wolfson JS,Swartz MN,Hooper DC. Pasteurella multocida infections. Medicine 1984; 63: 133– 154. 3 Beyt BE,Sondag J,Roosevelt TS,Bruce R. Human pulmonary Pasteurellosis. JAMA 1979; 242: 1647– 1648. 4 Stein AA,Fialk Ma,Blevins A, et al. Pasteurella multocida septicemia. Experience at a cancer hospital. JAMA 1983; 28: 508– 509. 5 Westbrook CA,Golde DW. Clinical problems in hairy cell leukemia: Diagnosis and management. Semin Oncol 1984; 11: 514– 522. 6 Raffi F,Barrier J,Baron D, et al. Pasteurella multocida bacteremia: Report of thirteen cases over twelve years and review of the literature. Scand J Infect Dis 1987; 19: 385– 393. 7 Athar MK,Karin MS,Mannam S,Ahmed M. Fatal Pasteurella sepsis and hairy-cell leukemia. Am J Hematol 2003; 72: 285. 8 Yokose N,Dan K. Pasteurella multocida sepsis, due to a scratch from a pet cat, in a post-chemotherapy neutropenic patient with non-Hodgkin lymphoma. Int J Hematol 2007; 85: 146– 148. 9 Davidovich T,Rimbroth S,Chazan B, et al. Recurrent septicemia and osteomyelitis caused by Pasteurella multocida in a patient with chronic lymphatic leukemia. Isr Med Assoc J 2008; 10: 653– 654. 10 Wadhwa PD,Morrison VA. Infectious complications of chronic lymphocytic leukemia. Semin Oncol 2006; 33: 240– 249. 11 Hainsworth JD,Litchy S,Barton JH, et al. Single agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: A phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21: 1746– 1751. Volume85, Issue2February 2010Pages 144-145 ReferencesRelatedInformation

Lung cancer: moving forward with tailored strategies

The toxicity profile of platinum-based chemotherapy for the treatment of non-small-cell lung cancer (NSCLC) is an ongoing concern for physicians. However, the introduction of new active drugs has allowed research into non-platinum-containing combinations. Several trials have been done comparing platinum-based and non-platinum-based regimens, and two meta-analyses have been published, which show 1-year overall survival only slightly favouring platinum-based regimens. 1 D'Addario G Pintilie M Leighl NB Feld R Cerny T Shepherd FA Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol. 2005; 23: 2926-2936 Crossref PubMed Scopus (323) Google Scholar , 2 Pujol JL Barlesi F Daurès JP Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials. Lung Cancer. 2006; 51: 335-345 Summary Full Text Full Text PDF PubMed Scopus (108) Google Scholar When considering the reported findings of four phase III trials (overall n=1683), 3 Kosmidis PA Kalofonos HP Christodoulou C et al. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer. A phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008; 19: 115-122 Crossref PubMed Scopus (46) Google Scholar , 4 Greco FA Spigel DR Kuzur ME et al. Paclitaxel/carboplatin/gemcitabine versus gemcitabine/vinorelbine in advanced non-small-cell lung cancer: a phase II/III study of the Minnie Pearl Cancer Research Network. Clin Lung Cancer. 2007; 8: 483-487 Summary Full Text PDF PubMed Scopus (15) Google Scholar , 5 Comella P Filippelli G De Cataldis G et al. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101). Ann Oncol. 2007; 18: 324-330 Crossref PubMed Scopus (49) Google Scholar , 6 Kubota K Kawahara M Ogawara M et al. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol. 2008; 9: 1135-1142 Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar one of which is published in this issue of the The Lancet Oncology by Kubota and colleagues, 6 Kubota K Kawahara M Ogawara M et al. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol. 2008; 9: 1135-1142 Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar a change in this conclusion is unlikely. Indeed, none of these trials have shown better survival in favour of the non-platinum-containing regimens compared with the platinum-based treatments. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III studyAlthough platinum-containing regimens remain the standard treatment for advanced NSCLC, non-platinum regimens could provide equivalent efficacy with a different toxicity profile. Full-Text PDF

Irinotecan, Carboplatin, and Imatinib in Untreated Extensive-Stage Small-Cell Lung Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network

The tyrosine kinase KIT has variable expression in small-cell lung cancer (SCLC) and may be a prognostic factor. Imatinib targets KIT expression, providing rationale for studying its role in combination with chemotherapy in SCLC in a multicenter phase II trial. Patients with untreated extensive-stage SCLC received carboplatin area under the concentration-time curve of 4 on day 1; irinotecan 60 mg/m2 on days 1, 8, and 15; and imatinib 600 mg/day. Treatment cycles were 28 days. Patients remained on imatinib until progressive disease or significant toxicity. Between September 2002 and May 2004, 68 patients were enrolled in this multicenter trial. Median age was 60 years (range, 37-81). The objective response rate was 66% (95% confidence interval: 54%-76%). Median progression-free survival was 5.4 months (95% CI: 4.3-6.0 months). Median overall survival was 8.4 months (95% CI: 6.3-10.5 months). Thirty-five percent of patients were alive at 1 year. Grade 3/4 hematologic toxicity included neutropenia (43%), anemia (16%), and thrombocytopenia (9%). Grade 3 nonhematologic toxicity included diarrhea (19%), fatigue (24%), and nausea (26%). Forty-eight of 56 patients (86%) with available tumor specimens had KIT expression detected. KIT expression did not appear to correlate with progression-free survival or overall survival in a retrospective analysis. Irinotecan, carboplatin, and imatinib is a safe and generally well-tolerated regimen in patients with SCLC. However, the addition of imatinib did not improve results from those expected with chemotherapy alone.

Preoperative docetaxel and gemcitabine in resectable non-small cell lung cancer: A phase II trial of the Minnie Pearl Cancer Research Network

18100 Background: Preoperative chemotherapy may improve outcomes for patients (pts) with resectable non-small cell lung cancer (NSCLC) compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative gemcitabine (G) and docetaxel (D) in pts with resectable NSCLC. Methods: The primary endpoint was to assess the pathologic response rate of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station = 2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Additional eligibility criteria: measurable disease, ECOG PS 0–1, and informed consent. Treatment: G 1,000 mg/m2 and D 30 mg/m2 days 1, 8 every 21 days x 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. If pts were inoperable, had incomplete resections, or N2 disease, D 20 mg/m2, carboplatin AUC=1.5 weekly x 7, and radiation to 63 Gy were administered. Analysis was by intent to treat. Results: Between April 2004 and September 2005, 75 pts were enrolled. Median age was 62 years. 92% of planned preoperative therapy was administered and 38 pts (51%) underwent resection. The clinical objective response rate was 30% (95% CI 20%-42%). No pathological complete responses were observed. 26 pts went on to receive chemoradiotherapy. Median progression-free survival was 9.8 months (95% CI 5.9–13.9). Median overall survival was 18 months (95% CI 14.8- 21.3). 71% of pts were alive at 1 year. Grade 3/4 hematologic toxicity with preoperative therapy included neutropenia (28%), anemia (4%), and thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity was limited. Conclusions: G/D is a well tolerated preoperative regimen for pts with resectable NSCLC, however did not result in pathologic complete responses. There is no suggestion that G/D is more active than other tested combined modality regimens. The role of preoperative therapy in NSCLC remains undefined. Additional studies comparing preoperative and adjuvant treatment are warranted. No significant financial relationships to disclose.

Weekly docetaxel versus docetaxel/gemcitabine in elderly/poor performance status (PS) patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC): Randomized phase III trial of the Minnie Pearl Cancer Research Network

7534 Background: Standard treatment for pts with good PS stage IIIB/IV NSCLC currently includes a two-drug platinum-based chemotherapy regimen. Optimum treatment for elderly and/or poor PS pts is less well defined, with some studies showing comparable efficacy/decreased toxicity with single agent treatment. In this randomized phase III trial we compared single agent weekly docetaxel with the combination of docetaxel/gemcitabine. Methods: Between 8/01 and 3/06, 350 pts were enrolled from 39 sites. Eligibility: previously untreated stage IIIB/IV NSCLC; age = 65 years and/or ECOG PS2; measurable disease; no active CNS metastases; adequate kidney, liver, marrow function; informed consent. Pts were randomized to receive docetaxel (36 mg/m2 IV days 1, 8, 15; repeated every 28 days) or docetaxel (30 mg/m2)/gemcitabine (800 mg/m2) both given days 1, 8, 15 of a 28-day cycle. Pts were reevaluated after 8 weeks; responders continued treatment for 6 cycles or until disease progression. Accrual of 330 evaluable pts allowed detection of improvement in 1-year survival from 25% (expected with weekly docetaxel) to 40% (significance level 0.05, power 0.8). Results: Clinical features of pts receiving docetaxel/gemcitabine (n=174) vs. weekly docetaxel (n=171) were similar; 19% were ECOG PS2, and 38% were > 75 years old. After a median follow-up of 22 months, there were no differences between docetaxel/gemcitabine vs weekly docetaxel in median survival (5.6 vs. 5.1 months; p=0.65) or 1-year survival (26% vs. 24%). TTP was prolonged with docetaxel/gemcitabine vs. docetaxel (4.8 months vs. 2.9 months; p=0.0004). Response rates: docetaxel/gemcitabine 25%; docetaxel 17%. Both regimens were well tolerated by most pts; grade 3/4 neutropenia, thrombocytopenia, and anemia were more frequent with docetaxel/gemcitabine. Conclusions: These two regimens have similar efficacy in these elderly/poor PS pts; weekly docetaxel produced less myelosuppression. However, these results in this relatively unselected community-based population emphasize the need for novel treatment approaches. No significant financial relationships to disclose.

Targeted treatments active against CUP

Patients with refractory carcinomas of unknown primary site (CUP) respond to a combination of bevacizumab and erlotinib according to results from a multicentre phase II study done by the Minnie Pearl Cancer Research Network (J Clin Oncol 2007; 25: 1747–52).

Phase II Trial of Bevacizumab and Erlotinib in Carcinomas of Unknown Primary Site: The Minnie Pearl Cancer Research Network

Treatment remains poor for many patients with carcinoma of unknown primary site (CUP), and no effective second-line treatment has been identified. Combination inhibition of vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) with bevacizumab and erlotinib has proved efficacious and well tolerated in other solid tumors. We therefore have evaluated the efficacy and toxicity of this combination in patients with CUP. Patients with CUP who either had received previous chemotherapy or were previously untreated with poor-prognosis clinical features were eligible for this study. All patients received bevacizumab 10 mg/kg IV every 2 weeks, along with erlotinib 150 mg orally daily. Patients were re-evaluated after 8 weeks of treatment; those with objective response or stable disease continued treatment until disease progression. Forty-seven (92%) of 51 patients received at least 8 weeks of treatment. Five patients (10%) had partial responses, and 29 patients (61%) had stable disease as the best response. The median survival for the entire group was 7.4 months, with 33% of patients alive at 1 year. This regimen was well tolerated by most patients. The combination of bevacizumab and erlotinib has substantial activity in the treatment of patients with CUP. The median survival is superior to survival previously reported with second-line chemotherapy, and is similar to the results of many first-line chemotherapy trials in this setting. This regimen merits further evaluation in patients with CUP.

Weekly Docetaxel and Bortezomib as First-Line Treatment for Patients with Hormone-Refractory Prostate Cancer: A Minnie Pearl Cancer Research Network Phase II Trial

Background Docetaxel is currently the standard first-line treatment in patients with hormone-refractory prostate cancer (HRPC). Bortezomib, the first proteasome inhibitor in clinical use, demonstrated activity against prostate cancer in phase I trials. For this reason, we evaluated the efficacy of docetaxel plus bortezomib in the first-line treatment of patients with HRPC. Patients and Methods Between February 2004 and May 2005, 63 eligible patients entered this phase II trial. All patients had metastatic adenocarcinoma of the prostate that had progressed on hormonal therapy. All patients received docetaxel 30 mg/m 2 and bortezomib 1.6 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after 8 weeks of treatment; responding and stable patients continued treatment until tumor progression. Results Sixty patients (95%) received ≤ 2 courses of treatment and were evaluable for response. Fifteen patients (25%; 95% confidence interval, 15%–38%) had a > 50% decrease in serum prostate-specific antigen level with treatment; the median response duration was 8 months. The median progression-free and overall survival times for the entire group were 4.1 months and 13.8 months, respectively; 20% of patients were alive at 2 years. The regimen was well tolerated, with uncommon grade 3/4 toxicity. Conclusion Treatment with this combination of weekly docetaxel and bortezomib showed no suggestion of improved efficacy versus previous results with docetaxel alone. Bortezomib has minimal activity in patients with HRPC and is unlikely to make any impact on treatment efficacy.

Phase II Trial of Paclitaxel, Carboplatin, and Etoposide in Advanced Poorly Differentiated Neuroendocrine Carcinoma: A Minnie Pearl Cancer Research Network Study

To evaluate the efficacy of chemotherapy with paclitaxel, carboplatin, and etoposide in advanced adult poorly differentiated neuroendocrine carcinomas. Patients eligible for this multicenter, phase II trial had metastatic poorly differentiated neuroendocrine carcinoma and had received no previous treatment. Patients with a variety of known primary sites (excepting small-cell lung cancer) and patients with unknown primary site were eligible. Patients received four courses of chemotherapy with paclitaxel, carboplatin, and etoposide, administered at 3-week intervals. After completing four courses of treatment, patients with objective response or stable disease received three courses (24 weeks) of weekly paclitaxel. Seventy-eight patients were treated; 62% had unknown primary site. Forty-one patients (53%) had major responses (complete response rate, 15%), and five patients remain disease free from 18 to 66 months after therapy. Response rates were similar regardless of histology (small-cell v poorly differentiated carcinoma) or primary site. The median, 2-year, and 3-year survivals for the entire group were 14.5 months, 33%, and 24%, respectively. Myelosuppression was the major toxicity, as has been reported previously with this regimen. This prospective phase II trial provides additional evidence that this family of relatively uncommon carcinomas is initially chemosensitive, with a high overall response rate to combination chemotherapy and a minority of complete responses. The three-drug regimen evaluated in this trial is moderately toxic, and has no obvious efficacy advantages when compared with standard platinum/etoposide regimens. Treatment for advanced poorly differentiated neuroendocrine carcinoma should parallel treatments used for small-cell lung cancer.

Maintenance gefitinib (G) after chemoradiotherapy (CRT) in patients (pts) with unresectable stage IIIA/B non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N3 mediastinal nodes >4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m2 IV and gemcitabine 800 mg/m2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]

Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by maintenance bevacizumab (B) in the treatment (tx) of limited-stage small cell lung cancer (LS-SCLC): Update of a phase II trial of the Minnie Pearl Cancer Research Network

7085 Background: Targeting VEGF has proven to be an effective tx strategy in many solid tumors including non-small cell lung cancer. VEGF expression in SCLC provides rationale for studying B in addition to chemoradiotherapy. Methods: The endpoints of this multicenter community-based study were to assess the safety, response rate (RR), and progression-free survival (PFS) of I/C/RT followed by B in patients (pts) with LS-SCLC. Tx included: C AUC = 5 IV D1, I 50mg/m2 IV D1,8 Q 21D x 4 cycles, and RT 1.8 Gy daily to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. If no progressive disease (PD) pts received B 10 mg/kg IV Q 14D x 10 doses. Eligibility included: measurable disease, ECOG PS 0–1, informed consent, and no new brain metastases or bleeding. Results: Fifty-seven pts were enrolled from 8/03 to 10/04. Forty-five pts (79%) and 41 pts (72%) received planned tx with I/C/RT and B, respectively. The range of follow-up is 14–28 months. Baseline features: median age 65 years (42–80); male/female, 37%/63%; ECOG PS 0,1: 26%/74%. Grade (G) 3/4 non-hematologic toxicity: diarrhea (9%), DVT (4%), vomiting (11%), and fatigue (9%). G3/4 hematologic toxicity: neutropenia (37%), anemia (5%), and thrombocytopenia (13%). Only 9% of pts experienced G3/4 toxicity during B tx (1 pt each: DVT, hypokalemia, depression, pain, and colon perforation). There were 2 tx-related deaths (both from respiratory failure; 1 and 2 doses of B had been administered). Complete/partial responses were observed in 15 pts (26%)/31 pts (54%), respectively, for an overall RR of 80% (95% CI 70%-90%). Four pts had stable disease, and 5% had PD (4 pts were unevaluable.) 1- and 2-year PFS rates were 63% and 54%, respectively. 1- and 2- year overall survival (OS) rates were 71% and 29%, respectively. Median OS was 15 months. Conclusions: The safety, RR, and 1- and 2-year survival results of I/C/RT followed by B compare favorably with standard tx for LS-SCLC; and B may improve PFS. Assessing the role of B as maintenance tx in improving OS in this setting will require randomized trials. [Table: see text]

Weekly bortezomib in the treatment of patients (pts) with previously treated multiple myeloma: A phase II trial of the Minnie Pearl Cancer Research Network

7547 Background: Bortezomib, administered on a twice-weekly schedule, is now a standard part of treatment for patients with multiple myeloma. Weekly bortezomib schedules have shown activity in other cancer types, and are more convenient than twice weekly schedules. In this multicenter, community-based phase II trial, we evaluate the feasibility, toxicity, and efficacy of weekly bortezomib in pts with previously treated multiple myeloma. Methods: Eligibility criteria included a diagnosis of multiple myeloma treated with 1 or 2 previous systemic regimens (only 1 if first-line therapy included high-dose therapy); ECOG PS 0–2; creatinine < 2.0 mg/dL; WBC ≥ 3000/μL; ANC > 1000/μL; platelets ≥ 50,000/μL; no peripheral neuropathy > grade 1; informed consent. All pts received bortezomib 1.6mg/m2 IV on days 1, 8, 15, and 22 of each 5-week cycle. Pts were reevaluated at 10-week intervals; treatment continued for 8 cycles (40 weeks) or until myeloma progression. Results: Between 5/04 and 12/05, 37 pts entered this trial. Pt characteristics: median age 70 years; male/female, 20/17; 24 pts (65%) had received 2 previous regimens (previous high dose therapy, 2 pts); elevated β-2 microglobulin, 27 pts (73%). Of 26 pts evaluated, 13 pts (50%) had major responses, 11 pts (42%) stable disease, and 2 pts (8%) had progression. After a median follow-up of 7 months, projected median PFS is 9.6 months; overall survival at 1 year is 81%. Weekly bortezomib was well tolerated by most pts. Grade 3/4 toxicities included fatigue (21%), diarrhea (11%), neutropenia (7%), thrombocytopenia (4%), all others < 5%. No grade 3/4 neuropathy occurred. Only 1 pt required bortezomib dose reduction during treatment, and 2 pts discontinued treatment because of toxicity (myelosuppression, 1; fatigue/dehydration, 1). Conclusions: Weekly bortezomib is a convenient, well tolerated treatment for pts with previously treated multiple myeloma. Overall response rates with this schedule are similar to those previously reported with the standard twice-weekly schedule. Further followup is necessary to better evaluate the duration of response and the incidence of cumulative toxicities. [Table: see text]

Topotecan: Weekly intravenous (IV) schedule similar to standard 5-day IV schedule as second-line therapy for relapsed small cell lung cancer (SCLC)—A Minnie Pearl Cancer Research Network phase II trial

7083 Background: Topotecan IV weekly produces significantly less myelotoxicity than the standard 5-day IV schedule and appears as active as the 5-day schedule in patients (pts) with relapsed ovarian cancer. Topotecan 5-day IV schedule is the standard for second-line therapy for sensitive relapse SCLC. Methods: The primary endpoints of this phase II trial were to determine the response rate and toxicity of topotecan IV weekly as second-line therapy in patients with sensitive relapse (SR) and resistant relapse (RR) SCLC. Topotecan 4mg/m2 IV over 30 minutes for 12 consecutive weeks was planned. Dose modifications were made based on toxicity. Pts were evaluated for response after 4 weeks; at least 3 weekly treatments were required to be evaluable. Results: A total of 103 pts (59 SR; 44 RR) were enrolled: 56 men, 48 women; age range 42–86 (median 65); performance status 0=18, 1=69, 2=16, 3=1. 47 pts with SR and 34 pts with RR were evaluable for response by WHO criteria. For SR, 3 pts had partial response (6.4%, 95% CI 1.3%-17.5%), 17 pts had stable disease (7 had minor responses with tumor shrinkage of 39%, 27%, 21%, 20%, 20%, 7%, and 3%, respectively). Using RECIST criteria 5 pts had PR (13%, 95% CI 6%-25%). For RR, 1 pt had a CR (3%, 95% CI 0.1%-15.3%), 6 pts had stable disease (2 had minor responses with 36%, 5% tumor shrinkage). Grade 3/4 neutropenia/thrombocytopenia was seen in 17 and 22pts, grade 3 infection 6 pts; grade 3/4 fatigue 16 pts. There was 1 treatment-related death. Median and 1-year survival for all patients was 4.5 months (SR = 5.6 months; RR 3.2 months, p = 0.05) and 19% (SR = 22%; RR = 10%). There was no difference in survival for PR versus stable pts, and PR/stable had 1-year survival of 46% compared to PD of 9% (p < 0.0001). Conclusions: Topotecan IV weekly has similar activity to the standard 5-day IV schedule in SR SCLC, and considerably less myelotoxicity. These data support the weekly schedule for standard therapy of SR SCLC, and further study of weekly topotecan as a component of combination therapy for SCLC. [Table: see text]

Bevacizumab plus erlotinib in patients (pts) with carcinoma of unknown primary site: A phase II trial of the Minnie Pearl Cancer Research Network

3033 Background: Targeted therapies inhibiting tumor angiogenesis or the epidermal growth factor pathway have demonstrated efficacy in a variety of solid tumors. In this multicenter phase II trial, we evaluated the efficacy of combined targeted therapy with bevacizumab plus erlotinib in pts with carcinoma of unknown primary site. Methods: Eligibility criteria included: metastatic adenocarcinoma or poorly differentiated carcinoma of unknown primary site; 1 or 2 previous chemotherapy regimens (previously untreated pts were eligible only if considered poor candidates for chemotherapy due to advanced liver or bone metastases); measurable disease; ECOG PS 0–2; no previous anti-angiogenic or EGFR inhibitor therapy; no active brain metastases; no active thromboembolic disease or bleeding abnormalities; adequate organ function; informed consent. All pts received bevacizumab 10mg/kg IV q 2 weeks and erlotinib 150mg PO daily. Pts were evaluated for response after 8 weeks; treatment was continued until tumor progression. Results: 51 pts entered this clinical trial between 4/04 and 7/05. Pt characteristics: median age 57; male/female, 22/29; ECOG 0/1/2, 5/43/3; previous chemotherapy, 75%. 49 pts (96%) received at least 2 months therapy and were evaluable for response. Objective responses occurred in 4 pts (8%) (all ongoing at 5+ - 19+ months); 30 pts (59%) had stable disease/minor response. After median follow-up of 13 months, median progression-free survival for the entire group is 6.2 months. Median overall survival is 8.9 months, with 42% of pts alive at 1 year. 1-year survival for previously treated vs. untreated pts: 41% vs. 46%. Toxicity with this regimen was consistent with previous reports; other than fatigue (12%), no grade 3/4 toxicity was observed in > 10% of pts. Conclusions: The combination of bevacizumab and erlotinib has activity in pts with carcinoma of unknown primary site. Progression-free and overall survival results appear superior to our previous second-line results using a variety of chemotherapy regimens, and are similar to results with first-line chemotherapy. Future trials will evaluate bevacizumab/erlotinib as part of first-line therapy. [Table: see text]

Topotecan—Single agent activity in a weekly intravenous (IV) schedule for first-line therapy in poor prognosis extensive stage small cell lung cancer (SCLC): A Minnie Pearl Cancer Research Network phase II trial

17000 Background: Topotecan IV weekly produces significantly less myelotoxicity than the standard 5-day IV schedule and appears as active in patients (pts) with relapsed ovarian cancer. Topotecan 5-day IV schedule is the standard for second-line therapy for pts with sensitive relapse SCLC. Methods: The primary endpoints were to determine the response rate and toxicity of weekly topotecan IV in pts with previously untreated extensive stage SCLC who were elderly, with poor performance status (PS), or severe coexistent medical illness. Topotecan 4mg/m2 IV over 30 minutes for 12 consecutive weeks was planned. Dose modifications were made based on toxicity. Pts were evaluated for response after 4 weeks; at least 3 weekly treatments were required to be eligible. Results: 39 pts were enrolled: 21 men, 18 women; age range 60–90 (median 71); PS 0 = 2, 1 = 18, 2 = 19). 31 pts were evaluable by WHO criteria for response. 4 pts had partial responses (13%, 95% CI 4%-30%); 20 pts (65%) had stable disease (4 had minor responses with tumor shrinkage of 29%, 19%, 12%, and 5%); 7 pts had progressive disease (22%). 15 pts completed 12 weeks of therapy. Grade 3/4 neutropenia/thrombocytopenia was seen in 11 pts and 3 pts; grade 3 infection 4 pts; grade 3/4 fatigue 12 pts. A total of 225 weeks of therapy was administered with 32 weeks of treatment delay and 10% required dose reduction. There were no treatment-related deaths. The median and 1-year survival of PR/stable pts were 5.6 months and 24%. Conclusions: Topotecan IV weekly has activity and was relatively well tolerated as first-line therapy in this very poor prognostic group of pts with extensive stage SCLC. The therapeutic index is improved with weekly topotecan IV schedule in contrast to the 5-day IV schedule. Additional study of weekly topotecan in combination with other agents in SCLC is warranted. [Table: see text]

Brief duration rituximab(R)/chemotherapy (CNOP or CVP) followed by maintenance rituximab in elderly/poor performance status patients (pts) with diffuse large B-cell lymphoma (DLBCL): A phase II trial of the Minnie Pearl Cancer Research Network

7577 Background: R-CHOP is the standard first-line treatment for pts with DLBCL; however, some pts are poor candidates due to general debility, cardiac disease, or other medical problems. Maintenance R is not effective after full course R-CHOP chemotherapy for DLBCL (ECOG 4494), but improves outcome following CHOP alone. In this phase II trial, we evaluated short course R/chemotherapy, followed by maintenance R, in pts who were not candidates for full-course R-CHOP. Methods: Eligibility: previously untreated DLBCL; stage II-IV; ECOG PS 0–2; age ≥ 70 years or poor CHOP candidate; adequate kidney, liver, bone marrow function; no HIV infection; informed consent. Pts received 3 courses of R-CNOP (cyclophosphamide 500mg/m2, mitoxantrone 10mg/m2, vincristine 1.0mg/m2, prednisone 80mg PO days 1–5, rituximab 375mg/m2) followed by pegfilgrastim 6mg sq day 2, at 21-day intervals. Mitoxantrone was omitted for pts with EF < 40%. Pts with response/stable disease after chemotherapy began maintenance R (375mg/m2 weekly × 4 doses, administered at 6-month intervals × 4 courses). Results: 31 pts entered this trial between 5/03 and 11/05. Clinical characteristics: median age, 78 years; ECOG PS 2, 45%; IPI 3–5, 79%. 27 pts (87%) have completed short course R-chemotherapy; 20 pts (65%) are currently receiving maintenance R. After completion of R-chemotherapy, 17 pts (63%) had responses (9 CR/CRu, 8 PR); 10 pts had stable disease/minor response. After median 16 month follow-up, 29 of 31 pts (94%) are progression-free; actuarial 2-year PFS is 90%. The 2-year overall survival is 74%. 4 pts have died (progressive lymphoma 2, intercurrent illnesses 2). Grade 3/4 toxicities: neutropenia 38%, other toxicities < 10%, no treatment-related deaths. Conclusions: Short-course R-chemotherapy followed by maintenance R was active and well tolerated in a group of elderly, poor prognosis pts with DLBCL. In spite of modest CR/CRu rate; the 90% 2-year PFS suggests a role for maintenance R. If these findings persist with further followup, this approach is worthy of further study in this patient group. [Table: see text]

Long-term follow-up and compilation of two trials utilizing concurrent paclitaxel/carboplatin/infusional 5-FU/radiation therapy (RT) in patients with localized esophageal cancer involved in the Minnie Pearl Cancer Research Network

4028 Background: The role of preoperative chemoradiation in patients (pts) with localized esophageal cancer remains unclear. Most preoperative regimens produce 20–30% pathologic complete response (pCR) rates, which predicts improved survival. Our community-based multicenter group performed sequential trials evaluating a novel paclitaxel-containing preoperative chemoradiation regimen, now with median followup > 6 years. Methods: Eligibility: untreated adenocarcinoma or squamous carcinoma of esophagus or GE junction; clinical stage I-III; surgical candidate; ECOG PS 0–2, adequate organ function; informed consent. Pts received paclitaxel 200mg/m2 IV and carboplatin AUC 6.0 IV, days 1, 22; 5FU 225mg/m2, 24 hr continuous infusion, days 1–42; RT 45 Gy in 1.8 Gy/d single daily fractions. Surgical resection was performed 6–10 weeks after completion. Results: 226 pts with the following characterstics were treated: median age 58 years; adenocarcinoma 74%; distal/GE junction 79%; clinical stage II/III 84%. 220 pts (97%) completed preoperative therapy, and 199 pts (88%) had resection. Responses in resected pts: pCR 45% (39% of entire group), PR (microscopic residual) 29%, PR (macroscopic) 15%. After median followup of 75 months, median PFS and overall survival for the entire group were 19 and 26 months, respectively; 3- and 5-year survivals were 40% and 33%, respectively. Median survival was better in pts with pCR vs others (33 vs 21 mo; p=.026). 3-yr survival comparisons of other potential prognostic factors: adeno vs squamous, 43% vs 42%; clinical stage I vs II/III, 63% vs 36% (p=.001); distal location vs others, 38% vs 45% (p=.45). Toxicity data have been previously published; overall 13 pts (6%) had treatment-related death (preop 2, postop 11). Conclusions: This preoperative combined modality regimen was feasible and highly active in a community-based setting. This is one of the largest series of patients treated with an identical preoperative approach and with long-term followup is curative in one-third of pts with localized esophageal cancer. [Table: see text]

Preoperative gemcitabine (G) and docetaxel (D) in patients (pts) with stage IB, II, or III non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network

17007 Background: Preoperative chemotherapy may improve outcomes for pts with resectable NSCLC compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative G/D for pts with resectable NSCLC. Methods: The primary endpoint was to assess the response rate (RR) of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station ≤2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Treatment included: D 30 mg/m2 IV and G 1000 mg/m2 IV D1,8 Q 21D × 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. Eligibility included: measurable disease, ECOG PS 0–1, adequate organ function, informed consent. Analysis was by intent to treat. Results: Fifty-four pts were enrolled between 4/04 and 9/05. Baseline features include: median age 62 years (42–82); male/female, 44%/56%; ECOG PS 0/1: 50%/50%; adenocarcinoma (28%), squamous (43%), large cell (9%), mixed/not specified (20%); IB (30%), IIA (5%), IIB (19%), IIIA (33%), IIIB (13%). Forty-eight pts (91%) completed preoperative treatment and 32 pts (60%) underwent resection. Grade 3/4 hematologic and non-hematologic toxicities were limited to neutropenia (20%) and infection (8%), respectively. All other toxicities were <5%. There were no treatment-related deaths. Complete/partial responses for all pts were observed in 1 pt/16 pts, respectively, for an overall RR of 31% (95% CI 20%–44%). Twenty-five pts (46%) had stable disease, and 11% had progression (6 pts were unevaluable.) No pathological complete responses were observed in 32 resected pts. After a median follow-up of 12 months, actuarial 1-year progression-free survival and overall survival (OS) are 54% and 79%, respectively. Median OS has not been reached. Conclusions: G/D is a well-tolerated preoperative regimen for pts with resectable NSCLC with activity rivaling platinum-based regimens. Further follow-up and additional studies comparing preoperative and adjuvant treatment are needed to assess the benefit of this regimen. [Table: see text]

Topotecan, paclitaxel, and carboplatin in advanced ovarian cancer: A phase II trial of the Minnie Pearl Cancer Research Network

15015 Background: Topotecan (T) is standard therapy for patients (pts) with relapsed platinum refractory ovarian cancer (OC). The addition of T to paclitaxel/carboplatin (PC) may improve the first-line therapy for pts with stage III/IV OC. Methods: The primary endpoints were to assess the toxicity and response rate of TPC in previously untreated pts with advanced OC. Pts with previously untreated stage III/IV OC with performance (PS) 0 or 1, normal hematologic and organ function were eligible. Topotecan 1mg/m2 per day IV days 1, 2, and 3; paclitaxel 175mg/m2 IV on day 3 and carboplatin (AUC=5) IV on day 3 were administered at 21-day intervals for 6 cycles with standard dose modifications for toxicities. Responses were assessed clinically after 2 cycles and at completion of therapy. Second look laporatory (SLL) was required for pts without evaluable tumor. Results: 50 pts were enrolled: age range 27–79 (median 63); performance status 0=16, 1=34; suboptimal debulking surgery (tumor > 1 cm) 32; 70% high grade tumors. Intent to treat response rates: complete response (CR) 20 pts (40%); partial response (PR) 12 pts (24%); stable (S) 13 pts (26%); progression 2 pts (4%); not evaluable 3 pts (6%). 13 pts had SLL with 5 CR, 5 PR and 3 S. Toxicities included: grade 3/4 neutropenia/thrombocytopenia 84%/44%; grade 3/4 fatigue/infection 10%/10%; no treatment-related deaths. Median progression-free survival (PFS) for all pts was 13.6 months and 1-, 2-, 3-year PFS 60%, 42%, 36%. Median survival 33.9 months for all pts with 1-, 2-, 3-year survivals 90%, 65%, 49%. Conclusions: The combination of TPC is active and relatively well tolerated with PC given on day 3. The response rates, PFS, and survivals appear similar to standard regimens. Randomized prospective trials will be required to determine the value of T added to PC for first-line therapy of advanced OC. [Table: see text]

Induction chemotherapy + gefitinib followed by concurrent chemotherapy/radiation therapy/gefitinib for patients (pts) with locally advanced squamous carcinoma of the head and neck: A phase I/II trial of the Minnie Pearl Cancer Research Network

5543 Background: Concurrent chemotherapy/radiation therapy (RT) improves treatment outcome in pts with locally advanced unresectable squamous cancers of the head and neck. We previously reported a 51% 3-year disease-free survival with induction paclitaxel/carboplatin/5-FU followed by concurrent paclitaxel/carboplatin/RT. In this phase II trial, we added gefitinib, an EGFR inhibitor, to a similar chemoradiation regimen. Methods: All pts had squamous carcinoma of the head and neck, with at least one of the following: N1-N3 disease, T3 or T4 primary lesion, nasopharynx primary (except T1N0M0). Additional eligibility: no previous therapy, ECOG PS 0 or 1, adequate bone marrow, kidney, liver function; informed consent. All pts received initial docetaxel 60mg/m2 D1, 22; carboplatin AUC 5.0 D1, 22; 5-FU 200mg/m2, 24-hour CI, D1–43; gefitinib 250mg PO qd, D1–43. Beginning week 8, pts received RT, 1.8Gy single daily dose to total 68.4 Gy, and concurrent docetaxel 20mg/m2 weekly × 6 doses + gefitinib 250mg PO daily. At completion of therapy, pts were reevaluated with CT scans and endoscopy. Results: 45 pts entered this trial between 8/04 and 8/05. Pertinent clinical characteristics: clinical T3/T4, 17; N2/N3, 23. 42 pts (93%) completed induction chemotherapy. 34 pts (76%) have completed combined modality therapy and have been restaged. Response to treatment: 11 CR (32%); 18 PR (53%); 5 stable/progression (15%). After median follow-up 7 months, 9 patients (20%) have developed progressive cancer. Actuarial PFS and OS at 1 year are 68% and 86%, respectively. Grade 3/4 myelosuppression was common, and grade 3/4 mucositis occurred in all pts during combined modality therapy. One pt had a treatment-related death during combined modality therapy. The addition of gefitinib did not substantially increase toxicity. Conclusions: This combined modality regimen was feasible and produced high response rates in pts with locally advanced head and neck cancer. Toxicity was consistent with other effective combined modality regimens for these pts. Further follow-up is needed to better assess the benefit of this approach. [Table: see text]