Part 7 of a 12-Part Series

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1 Release Date: June 1, Publication Date, Part 7: September 1, Termination Date: December 31, Estimated time to complete this 12-part newsletter series: 3.0 hours. Each newsletter in this 12-part series is worth.25 credit for a total of 3.0 credits. For additional updates, go to Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations Part 7 of 12: Lung Adenocarcinoma with Solitary Adrenal Metastasis in a 71-Year-Old Man Dear Colleague: Non small-cell lung cancer (NSCLC) is the most common class of lung cancer, accounting for 75% to 80% of all lung cancer cases. NSCLC mainly comprises three histologies epidermoid or squamous, adenocarcinoma, and large cell carcinoma. Adenocarcinoma has overtaken squamous cell carcinoma as the most common histologic type. In cases of localized disease, surgical resection offers the best potential for cure. The best potential for response in distant metastatic disease, however, may require a variety of treatment modalities, including surgical resection, chemotherapy, or radiation therapy. The decision of which modalities to use and in what sequence is based on patient factors, such as performance status and co-morbidities, and tumor factors, such as site of metastasis. This Tx Reporter presents the case of a 71-year-old man with stage IV adenocarcinoma with a solitary distant adrenal metastasis. This case discussion highlights the need for disease management based on the patient s presentation, as well as the clinical decisions unique to a solitary adrenal mass. We are pleased to offer you part 7 of the 12-part series, Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations. These case-based newsletters, designated for.25 CME credit each, will comprise discussions about gynecologic cancers and lung cancer. Presentations of patient cases and discussion of relevant treatment dilemmas and options by a distinguished faculty of oncologists are designed to update you on the latest clinical trial results and their implications for clinical practice. We hope you find this series helpful and informative, and that the discussions will assist you in incorporating this information into your clinical practice. Sincerely, Chair Eric K. Rowinsky, MD Director, Clinical Research Institute for Drug Development Clinical Professor of Medicine University of Texas Health Sciences Center San Antonio, Texas Faculty Michael B. Dabrow, DO Associate Professor of Medicine Chief, Division of Medical Oncology University of Medicine and Dentistry of New Jersey School of Osteopathic Medicine Stratford, New Jersey Part 7 of a 12-Part Series Patient Presentation Mr. K is a 71-year-old mechanical engineer with a history of chronic obstructive pulmonary disease (COPD) and tobacco use (60 pack-years). He presented to his pulmonologist with complaints of weakness, dyspnea on exertion, and fever (101 F). Despite his symptoms and a 5-lb weight loss, he had continued working up until the time of the office visit and did not appear cachectic at 170 lb. He had no history of postural hypotension, and no previous chest x-rays were available. Mr. K was admitted to the hospital, where an elevated white blood count (13,100/mm 3 ) was found and a chest x-ray showed a postobstructive pneumonia/atelectasis in the right upper lobe. A computed tomography (CT) scan identified a large obstructing right-upper lobe mass with postobstructive infiltrate, suspicious of malignancy, and a single adrenal mass. After 5 days of antibiotics, Mr. K s fever persisted at F and chest x-ray showed no improvement. Mr. K s pulmonologist believed this pneumonia would not resolve with antibiotics alone and a thoracic surgery consultant recommended biopsy of the area. Fineneedle aspiration (FNA) biopsies of the lung and adrenal gland were performed and both revealed adenocarcinoma. Mr. K underwent right upper lobectomy, secondary to postobstructive pneumonia. Pathology revealed a 5-cm adenocarcinoma, moderately well differentiated, with negative margins and metastasis to ipsilateral hilar lymph nodes only. Mr. K s postoperative Eastern Cooperative Oncology Group (ECOG) performance status was 1. His complete diagnosis was stage IV moderately well-differentiated adenocarcinoma T2, N1, M1. Case continues, page 2, column 2 Download this 12-part series, Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations, available at

2 REPORTER SM : ONCOLOGY Target Audience This activity is designed for oncologists and oncologic healthcare professionals who treat patients with gynecologic or lung cancer. Activity Goal The goal of this activity is to review the most recent clinical trial results on innovative sequencing strategies, and on unique chemotherapy combinations in the treatment of gynecologic cancers and lung cancer, using a case-based learning method. Learning Objectives After completing this activity, the participant should be able to: Compare the efficacy and safety of available regimens for treating recurrent gynecologic and lung cancers. Consider the risks and benefits of extending the platinum-free interval and its impact on future responses to additional treatment regimens. Formulate a treatment strategy that maximizes outcomes and reduces toxicity through judicious sequencing of therapies and dosing schedules when treating patients with platinum-sensitive, recurrent gynecologic or lung cancer. Discuss future clinical applications, including activity and toxicity profiles, of novel combinations and schedules of chemotherapies, including topoisomerase inhibitors, alone or in combination with platinum agents, in the treatment of gynecologic and lung cancer. CME Information Projects In Knowledge is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. This 12-part newsletter is planned and implemented as an independent CME activity in accordance with the ACCME Essential Areas and Policies. Projects In Knowledge designates this educational activity for a maximum of 3.0 Category 1 credits toward the AMA Physician s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. To receive documentation of your participation in each newsletter for.25 hour of CME credit, you must achieve a passing score of 70% or higher on each of the 12 posttests. Full instructions for submission are included on the posttest accompanying each CME newsletter. After passing the posttest, you will be issued a CME certificate of.25 credit. Disclosure The Disclosure Policy of Projects In Knowledge requires that the faculty participating in a CME activity disclose to the audience any significant relationship they may have with a pharmaceutical or medical equipment company, product, or service that may be mentioned as part of their presentation, as well as any relationship with the funder of this activity. Michael B. Dabrow, DO, has indicated no significant relationships with industry. Eric K. Rowinsky, MD, has received grant/research support from Aventis Pharmaceuticals, Daiichi Pharmaceutical Corporation, Eli Lilly and Company, GlaxoSmithKline, OSI Pharmaceuticals, Inc, Pfizer Inc, and Wyeth-Ayerst Pharmaceuticals. The opinions expressed during this 12-part activity are those of the faculty and do not necessarily reflect those of Projects In Knowledge or the funder. This activity may include a discussion of therapies that are unapproved for use or investigational, ongoing research, or preliminary data. This CME activity is provided by Projects In Knowledge solely as an educational service. Specific patient care decisions are the prerogative of the physician caring for the patient. This independent CME activity is supported by an educational grant from GlaxoSmithKline. Copyright 2003, Projects In Knowledge, Inc. Little Falls, NJ All rights reserved. 2 Selecting First-Line Therapy Question 1: What treatment option would you recommend for Mr. K? a. Cisplatin/gemcitabine b. Carboplatin/paclitaxel c. Radiation to adrenal gland d. Palliative care e. a or b Discussion (e) In the United States, first-line treatment for patients with stage IV NSCLC and a good ECOG performance status (0 or 1) is typically systemic chemotherapy, usually with a platinumbased regimen. 1 Management of disease, however, must be tailored to the patient s presentation, as well as to the facilitation of future therapy. Mr. K s unusual presentation of a postobstructive pneumonia that would not resolve with standard therapy required adjustment to the initial handling of his disease, prior to chemotherapy. Although surgical extirpation of the primary tumor is not standard treatment for metastatic NSCLC, it was necessary for this patient and served two purposes. First, it was the only means to clear the refractory pneumonia. Second, by removing the concurrent infection, it removed Mr. K s only contraindication to the standard myelosuppressive chemotherapeutic regimen for NSCLC. Mr. K s right upper lobectomy, therefore, was essential before his first round of chemotherapy. A number of platinum doublet combinations are used in the treatment of advanced NSCLC. In the large (N = 1155) phase 3 trial, ECOG 1594, the efficacy and toxicity of four platinum-based doublets (cisplatin/paclitaxel, cisplatin/ gemcitabine, cisplatin/docetaxel, and carboplatin/paclitaxel) were compared in patients with advanced NSCLC. 2 Although none of the doublets distinguished itself as superior in efficacy, carboplatin/paclitaxel demonstrated a lower toxicity profile. The overall response rates (complete or partial) varied only from 16% to 21%, and the median survival was similar at 7.4 to 8.1 months. The cisplatin/ gemcitabine arm of the study demonstrated the longest median time to progression (4.2 months), but was associated with grade 3, 4, or 5 renal toxicity in 9% of patients and grade 3 or 4 thrombocytopenia in 50% of patients. Neurotoxicity was seen in 9% and 10% of patients treated with cisplatin/gemcitabine and carboplatin/ paclitaxel, respectively. Some clinicians believe that nonplatinum front-line therapy is an attractive alternative to platinum-based therapy, offering equivalent efficacy with lower toxicity. Greek researchers 3 found carboplatin/paclitaxel was as effective as gemcitabine/paclitaxel in patients with advanced NSCLC. Early data from an ongoing US study 4 comparing gemcitabine/carboplatin and gemcitabine/paclitaxel with carboplatin/ paclitaxel in advanced NSCLC show that response rates are similar. Despite these data on nonplatinum front-line therapy, data from other studies 5, 6 continue to support the majority opinion of lung cancer experts that platinum-containing combinations produce a superior response rate. Within the context of metastatic disease, a solitary adrenal mass may have some positive prognostic significance. Of the approximately 50% of patients with NSCLC who initially present with metastatic disease at diagnosis, only about 7% present with a solitary metastasis to the brain, lung, liver, bone, or adrenal gland. 7 Data suggest that patients with a solitary metastasis have in general a better prognosis than patients with multiple metastases. In addition, patients with a solitary adrenal metastasis may have the option of adrenalectomy. Several case reports have shown that adrenalectomy for a solitary adrenal metastasis has impressive survival for those individuals In light of Mr. K s excellent performance status and solitary adrenal metastasis, treatment should not be limited to palliative care alone, which would not offer him the therapeutic benefit that he 12, 13 may gain from systemic chemotherapy. Radiation to the adrenals may achieve a response in the adrenal mass, but is not recommended due to the likelihood of significant nephrotoxicity and lack of supporting data. Case Continues Mr. K was started on a carboplatin/ paclitaxel combination regimen for two cycles. After the second cycle, therapy was stopped because CT scan showed that the adrenal tumor had grown to 5.0 cm. In addition, his ECOG performance status had decreased to 2.

3 TREATMENT REPORTER Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations Selecting Second-Line Treatment Question 2: In light of Mr. K s progression and decreased performance status, what further systemic treatment option would you NOT recommend? a. Cisplatin/docetaxel b. Vinorelbine/gemcitabine c. Docetaxel alone d. Topotecan/gemcitabine e. Palliative care Discussion (a) Platinum-based second-line treatment can be ruled out based on Mr. K s failure to respond to platinumbased first-line treatment. Other current presenting factors that must be considered when selecting treatment at this point include his decreased performance status and advanced age. Patients with an ECOG performance status of 2 have been found to be poor candidates for platinum-based chemotherapy. ECOG 1594 initially included patients with a performance status of 2. 2 In the first 66 of these patients, toxic deaths were noted in 15% and 17% of the cisplatin/gemcitabine and cisplatin/docetaxel arms, respectively. 14 The study design, therefore, was altered to include a threshold ECOG performance status of 0 or 1. Patients aged >70 years may be less able to tolerate the toxicity of platinumbased therapy A number of studies have shown that nonplatinum single and combination options are available for patients who are either elderly or who have an ECOG performance status of 2, although no single study has specifically evaluated patients who were both elderly and with poor performance status. An analysis 18 of survival data from 120 elderly patients with advanced NSCLC found the efficacy of combination therapy to be superior to that of monotherapy. Gemcitabine/ vinorelbine produced higher overall response rates and increased median survival compared with vinorelbine alone: 22% and 29 weeks, respectively, for combination therapy; 15% and 18 weeks, respectively, for monotherapy. Single-agent therapies, however, are an attractive option due to their favorable response:toxicity profiles compared with combination regimens. The Elderly Lung Cancer Vinorelbine Italian Study (ELVIS) 19 demonstrated that patients who received vinorelbine have shown increased median survival (from 21 to 28 weeks, P =.03), fewer cancer-related symptoms, and higher QOL scores than patients who received best supportive care. 19 Similarly, the Multicenter Italian Lung Cancer in the Elderly Study (MILES) showed that patients receiving either gemcitabine or vinorelbine as monotherapy also have shown significantly better survival than patients receiving supportive care. 20 Shepherd et al 6 looked at single-agent docetaxel therapy in patients with progressive disease after platinum therapy. Twenty-four percent of patients across a range of ages had an ECOG performance status of 2 in this phase 2 trial. Median survival (7.5 versus 4.6 months, respectively) and 1-year survival (37% versus 11%, respectively) were significantly better with treatment with docetaxel (75 mg/m 2 ) compared with best supportive care. Hematologic toxicity was manageable at this dose, and grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, was similar in the two groups. In a phase 3 trial 5 of docetaxel versus vinorelbine or ifosfamide in platinum-refractory patients, docetaxel demonstrated an improved time to progression and 1-year survival. Seventeen percent of these patients had an ECOG performance status of 2. Elderly patients were also included in this study. In a phase 1-2 trial (N = 19), Rinaldi et al 21 used topotecan/gemcitabine (daily x 5 schedule) in previously treated patients (ages years). They reported an 18% response rate and a 32% stabilization of disease, but this schedule resulted in significant thrombocytopenia and neutropenia, the dose-limiting toxicities. Only 2 of 19 patients had an ECOG performance status of 2. Dabrow et al 22 used the topotecan/gemcitabine combination in a once-weekly schedule in a previously untreated patient population, with a median age of 70 years and ECOG performance status of 2 in 42%. This phase 1-2 study (N = 24) found the maximum tolerated dose was 2.0 mg/m 2 weekly for topotecan and 1250 mg/m 2 weekly for gemcitabine, with neutropenia as the dose-limiting toxicity, minimal nonhematologic toxicity, and the ability to give multiple cycles (maximum 13). The response rate was 21%, with two long-term survivors. Palliative care alone is a reasonable option for patients who have failed first-line therapy with a platinum-based regimen and are not willing or able to endure the potential toxicities of further treatment. Case Continues Mr. K was enrolled in a clinical trial and started on weekly topotecan 2.0 mg/m 2 and weekly gemcitabine 1250 mg/m 2 for six cycles (3 weeks on, 1 week off). A CT scan was performed after every two cycles. After the sixth cycle, a CT scan showed the adrenal lesion had decreased from a 5-cm mass to a 0.5-cm necrotic area and Mr. K s ECOG performance status had improved to 0. Considering Adrenalectomy Question 3: What treatment option would you now recommend? a. Continue current therapy b. Return to platinum-based therapy c. Bilateral adrenalectomy Discussion (c) In light of the patient s good response to therapy thus far, with no local recurrence of pulmonary disease and no metastases detected outside the adrenal gland, adrenalectomy may offer a benefit superior to that offered by less aggressive regimens, including continuation of current therapy, return to platinum-based therapy, or watchful waiting. In a study from Memorial-Sloan Kettering Cancer Center, 7 nine patients with adrenal metastases were followed. All six patients who were treated with chemotherapy alone died, whereas the three patients who had chemotherapy first, followed by pulmonary and adrenal resection, all survived the short follow-up period. In a review of the literature on the management of adrenal metastases in patients with NSCLC, Abdel-Raheem et al 23 reported a 19-month median survival in those treated with adrenalectomy followed by chemotherapy, compared with 15 months for those treated with chemotherapy alone, 14 months for those treated with adrenalectomy alone, and 8 months for those treated with palliative radiation alone. In an eightcenter French study, Porte et al 24 followed 43 patients with a solitary metastasis from NSCLC treated with resection of the metastasis. The median survival was 11 months and 3 patients were alive at 5 years. Although there is some precedent for performing adrenalectomy before chemotherapy, 25 there may be advantage to waiting until after chemotherapy to 3

4 perform adrenalectomy. Chemotherapy as first-line treatment gives opportunity for a chemosensitive adrenal mass to respond. In addition, most patients with a solitary adrenal metastasis will develop other metastatic disease. Postponing surgery allows surgery to be avoided completely if additional metastatic sites develop during chemotherapy. Continuation of current therapy was not considered the best option for Mr. K, as he had already achieved a maximum response and there is no known benefit of additional chemotherapy once maximum response has been achieved. Despite his age, switching to a platinumbased therapy would be reasonable based on Mr. K s improved performance status and approximately 5-month platinum-free interval. Monitoring Mr. K holds open the options of returning to platinum-based therapy, restarting topotecan/gemcitabine, or beginning another regimen if disease progresses. Although the options of continuing treatment or switching to platinum are both reasonable, the option of adrenalectomy may offer Mr. K a potential survival advantage. Case Continues Mr. K underwent a bilateral adrenalectomy, and no viable tumor was found. He tolerated surgery well and began corticosteroid replacement therapy. After a standard postsurgical recuperative period, he returned to work part time. At 35 months postdiagnosis, Mr. K is alive with no evidence of disease recurrence. Summary Treatment choices must take into consideration not just the type and stage of cancer, but importantly, the patient s presentation, performance status, and age. The patient s initial presentation may necessitate thinking outside of prescribed guidelines in order to position the patient on a trajectory for subsequent successful treatment. A good to excellent performance status qualifies a patient for a broader range of therapeutic options, such as standard platinum-based therapies, which can be toxic to a patient with an ECOG performance status of 2. Advanced age, particularly when combined with a poor performance status, also limits treatment options due to concerns about toxicity and comorbidities among the elderly. For these patients, nonplatinum single-agent or combination regimens offer effective alternatives to platinum. TX 4 References 1. Ettinger DS, Kris MG. NCCN: Non-small cell lung cancer. Cancer Control. 2001;8(6 suppl 2): Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346: Kosmidis P, Mylonakis N, Nicolaides C, et al. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2002;20: Treat J, Belani CP, Edelman M. A randomized phase III trial of gemcitabine (G) in combination with carboplatin (C) or paclitaxel (P) versus paclitaxel plus carboplatin in advanced (Stage IIIB, IV) non-small cell lung cancer (NSCLC) (abstract 2511). Presented at: 2003 American Society of Clinical Oncology (ASCO); May 31-June 3, 2003; Chicago, IL. 5. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18: Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18: Burt ME. Role of surgery in the treatment of patients with solitary metastasis from non-small cell lung cancer. In: Aisner J, Green OP, Perry MC, eds. Comprehensive Textbook of Thoracic Oncology. Baltimore: Lippincott, Williams & Wilkins; 1996: Ettinghausen SE, Burt ME. Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer. J Clin Oncol. 1991;9: Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: Rosenberg SA, ed. Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia: Lippincott, Williams & Wilkins; 1997: Raviv G, Klein E, Yellin A, Schneebaum S, Ben-Ari G. Surgical treatment of solitary adrenal metastases from lung carcinoma. J Surg Oncol. 1990;43: Reyes L, Parvez Z, Nemoto T, Regal AM, Takita H. Adrenalectomy for adrenal metastasis from lung carcinoma. J Surg Oncol. 1990;44: Marino P, Pampallona S, Preatoni A, Cantoni A, Invernizzi F. Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest. 1994;106: Rapp E, Pater JL, Willan A, et al. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer report of a Canadian multicenter randomized trial. J Clin Oncol. 1988;6: Johnson D, Zhu J, Schiller J, et al. E1594 A randomized phase III trial in metastatic non-small cell lung cancer (NSCLC) outcome of PS 2 patients (Pts): an Eastern Cooperative Group Trial (ECOG) (abstract 1779). Presented at: 1999 American Society of Clinical Oncology (ASCO); May 15-18, 1999; Atlanta, GA. 15. Basche M, Kelly K. Treatment of non-small-cell lung cancer in older persons. Oncology (Huntingt). 2003;17:31-39; discussion 43-34, Kelly K, Giarritta S, Akerley W, et al. Should older patients receive combination chemotherapy for advanced non-small cell lung cancer (NSCLC)? An analysis of Southwest Oncology Trials 9509 and Proc Am Soc Clin Oncol. 2001;20:329a. 17. Kubota K, Hosomura K, Kakinuma R, et al. Cisplatin nephrotoxicity in elderly patients with lung cancer. Proc Am Soc Clin Oncol. 1998;17:491a. 18. Frasci G, Lorusso V, Panza N, et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000;18: Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst. 1999;91: Gridelli C, Perrone F, Cigolari S, et al. The MILES (Multicenter Italian Lung Cancer in the Elderly Study) phase III trial: gemcitabine + vinorelbine vs gemcitabine in elderly advanced NSCLC patients. Proc Am Soc Clin Oncol. 2001;20: Rinaldi D, Lormand N, Brierre J, et al. A phase I-II trial of topotecan and gemcitabine in patients with previously treated, advanced non-small cell lung cancer (LOA-3). Cancer Invest. 2001;19: Dabrow MB, Francesco MR, Gilman PB, et al. Combined chemotherapy with topotecan and gemcitabine in patients with inoperable or metastatic non-small cell lung cancer. Cancer Invest. 2003;21: Abdel-Raheem MM, Potti A, Becker WK, Saberi A, Scilley BS, Mehdi SA. Late adrenal metastasis in operable non-small-cell lung carcinoma. Am J Clin Oncol. 2002;25: Porte H, Siat J, Guibert B, et al. Resection of adrenal metastases from non-small cell lung cancer: a multicenter study. Ann Thorac Surg. 2001;71: National Comprehensive Cancer Network. Non-small cell lung cancer. Clinical Practice Guidelines in Oncology. Version

5 CME Posttest Part 7 of 12 CME Instructions Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations To receive documentation of your participation in this 12-part CME activity (for which each newsletter equals.25 hour for a total of 3.0 hours of CME credit), please complete the following steps: 1. Read each newsletter carefully. 2. Complete the CME Posttest included in each of the newsletters, selecting the most appropriate response to each question. 3. Complete the Evaluation Survey included at the end of each newsletter. 4. Mail or fax each of your completed CME Posttests and Evaluations to Projects In Knowledge, Overlook at Great Notch, 150 Clove Road, Little Falls, NJ 07424; fax: by December 31, If you complete these steps and score 70% or higher, Projects In Knowledge will mail you an acknowledgment of participation for up to 3.0 hours of CME credit within 6 weeks of receipt of your materials. If you score lower than 70%, Projects In Knowledge will notify you by mail and you will be given another chance to take the Posttest. Name Degrees/Credentials Mailing Address City State ZIP Phone Fax Please indicate your answers below. 1. Cisplatin/gemcitabine is the standard therapy for all advanced non small-cell lung cancer. 2. Patients with advanced non small-cell lung cancer and an ECOG performance status of 2 should be treated with nonplatinum chemotherapy. 3. Patients with metastatic disease from non small-cell lung cancer limited to the adrenal gland should be considered for adrenalectomy. 4. Single-agent therapies provide a favorable response:toxicity profile compared with combination regimens, particularly for elderly patients or patients with an ECOG performance status of Weekly topotecan/gemcitabine in non small-cell lung cancer has minimal nonhematologic toxicity PT

6 CME Evaluation Survey Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations Name Degrees/Credentials Address City State ZIP Instructions: Please complete this survey, along with the CME Posttest, and mail or fax (both sides) to Projects In Knowledge, Overlook at Great Notch, 150 Clove Road, Little Falls, NJ 07424; fax: Please rate the extent to which you achieved the learning objectives: Excellent Very Good Good Satisfactory Poor Compare the efficacy and safety of available regimens for treating recurrent gynecologic and lung cancers. Consider the risks and benefits of extending the platinum-free interval and its impact on future responses to additional treatment regimens. Formulate a treatment strategy that maximizes outcomes and reduces toxicity through judicious sequencing of therapies and dosing schedules when treating patients with platinum-sensitive, recurrent gynecologic or lung cancer. Discuss future clinical applications, including activity and toxicity profiles, of novel combinations and schedules of chemotherapies, including topoisomerase inhibitors, alone or in combination with platinum agents, in the treatment of gynecologic and lung cancer. 2. Please rate the overall value of this enduring material: Strongly Strongly Agree Agree Disagree Disagree 3. Course was free from commercial bias: If you Disagree or Strongly Disagree, why?... Just Right Too Advanced Too Basic 4. Please rate the level of the material presented: 5. Please list any changes in your practice that you would consider making as a result of participating in this activity: ES Page 1 of 2

7 Name CME Evaluation Survey (cont d) Case Studies in Recurrent Gynecologic and Lung Cancer: Chemotherapeutic Innovations 6. Please rate your interest in self-directed or distance learning in the following formats: Very Interested Moderately Interested Not Interested a. Audioconference b. Videoconference c. Enduring materials (audiocassettes, videotapes, monographs) d. Internet (online discussions with experts, educational activities) e. Multimedia (online, CD-ROM) 7. Please tell us how long it took you to complete this course: Please list topics and/or experts you would find interesting and professionally relevant for future CME activities: 9. Follow-up: As part of our ongoing continuous quality-improvement effort, we conduct postactivity follow-up surveys to assess the impact of our CME courses on professional practice. Please indicate your willingness to participate in such a survey: Yes, I would be interested in participating in a follow-up survey. No, I m not interested in participating in a follow-up survey. Additional comments about this activity:... Thank You for Your Participation ES Page 2 of 2