A Chance Like This Only Comes at First Relapse

Choose Hycamtin for Injection as First Single Agent for Relapsed Ovarian Cancer

A Chance Like This

Only Comes At First Relapse Choose single-agent Hycamtin for Injection when ovarian cancer returns— because your choice may change her future.

Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

WARNING Hycamtin (topotecan HCl) for Injection should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. Therapy with Hycamtin for Injection should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3.

In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection and death, frequent peripheral blood cell counts should be performed on all patients receiving Hycamtin for Injection.

Please see accompanying full Prescribing Information, including BOXED WARNING.

Keep all her options open

A Chance Like This

Only Comes At First Relapse

In the treatment of RELaPSED ovarian cancer

Maximize Available Therapies to Reach Long-Term Goals— Treat Relapsed Ovarian Cancer With a Nonplatinum Single Agent to...

Maximize efficacy Extending patients’ platinum-free interval by using a nonplatinum agent increases the probability of response to platinum reinduction at the next relapse.1,2 • Responses to platinum retreatment are generally <35% in patients who relapse after 6 to 24 months1,3 • The response increases to ~60% in patients who relapse after 24 months1,3 Responses to Platinum Retreatment According to Length of Platinum-Free Interval1,3 ≤12 months

>12 to ≤24 months

70

RESPONSE RATE (%)

59%

57%

60

>24 months

50 40

27%

30 20

27%

33%

17%

10 0

GORE ET AL (N=54)* MARKMAN ET AL (n=72)† DURATION OF PLATINUM-FREE INTERVAL/STUDY INVESTIGATOR

* Open-label trial of patients who relapsed following initial treatment with cisplatin or carboplatin and were either crossed over to the other platinum compound (n=43) or re-treated with the same drug (n=11). † Retrospective analysis of patients who relapsed after ≥2 platinum-based regimens (N=82): 12 patients had received 3 platinum regimens; 72 patients were evaluable for response. NOTE: the platinum-free interval was extended by using a nonplatinum agent; 29 patients received a course of nonplatinum-based therapy between platinum regimens.

Avoiding multidrug resistance may control disease progression and prolong survival.

• Patients who were responsive to first-line platinum-taxane therapy may become resistant or refractory to 1 or both agents during retreatment2 •N onplatinum agents may be less efficacious (and more toxic) when used as salvage therapy (eg, at third or fourth relapse)4 2

Maximize response

Minimize toxicity The development of cumulative toxicities may compromise retreatment with first-line agents, especially in4,5: â&#x20AC;˘ Older patients â&#x20AC;˘ Patients with preexisting neurologic, hematologic, or renal toxicities Goals for Long-Term Treatment Success2,5

Control disease progression

Prolong survival

Maintain platinum sensitivity

Control disease-related symptoms

Minimize cumulative side effects

Maintain quality of life

Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Please see accompanying full Prescribing Information, including BOXED WARNING. Keep all her options open

CHOOSE

AS FIRST SINGLE AGENT FOR RELAPSED OVARIAN CANCER

Hycamtin for Injection

In the treatment of RELAPSED ovarian cancer

Hycamtin for Injection as First Single Agent— the Right Treatment at the Right Time Can Make a Difference • FDA approved in 1996, Hycamtin for Injection has more than a decade of clinical experience and is 1 of the most clinically researched single agents in relapsed ovarian cancer*6-12 Overview of Clinical Trials With Hycamtin for Injection in Relapsed Ovarian Cancer Author (journal, year)

Number of Patients

Overall Response †

Stable Disease‡

Clinical Benefit §

Median TTP

235#

17.0%

40.4%

57.4%

N/A

56.7

McGuire8

46

32.6%

47.8%

80.4%

10.0

80.8**

Bookman9 (JCO, 1998)

139#

13.7%

27.3%

41.0%

12.1

47.0

ten Bokkel Huinink10

112#

20.5%

29.5%

50.0%

23.1

61.3

Kudelka11

30#

13.3%

56.6%

69.9%

N/A

40.0

Creemers12

92

16.3%

20.7%

37.0%

11.9

N/A

Gordon6,7

(Gynecol Oncol, 2004; JCO, 2001) (JCO, 2000)

(JCO, 1997)

(JCO, 1996)

(JCO, 1996)

*A PubMed search on August 1, 2008, with the parameters of “topotecan, ovarian cancer, and clinical trials” listed 147 studies. † Responses (partial response, complete response, and stable disease) independently confirmed. ‡ Stable disease was defined as any measurement that did not fulfill the criteria of response or progression and lasted at least 8 weeks.

(NOTE: Kudelka study defined stable disease as “a steady state or <partial response with no disease progression for at least 3 weeks.”) § Clinical benefit=overall response rate + stable disease.  TTP=time to progression (weeks). ¶ Weeks. # Intent-to-treat population. **Median value not reached at time of publication.

N/A=not assessed.

4

Median Survival¶

Increasing the platinum-free interval by using a nonplatinum agent may increase the probability of response to platinum reinduction at next relapse.1,2

Overview of Clinical Benefit With Hycamtin for Injection in Relapsed Ovarian Cancer Stable disease

Overall response

CLINICAL BENEFIT (%)

100

80.4

80

69.9

60 40

50.0 37.0 20.7

41.0

56.6

57.4 40.4

29.5

27.3 32.6

20 0

47.8

16.3

13.7

CREEMERS

BOOKMAN

20.5 TEN BOKKEL HUININK

17.0 GORDON

13.3 KUDELKA

MCGUIRE

In a retrospective analysis, stable disease and partial response were associated with a survival benefit vs progressive disease in patients treated with Hycamtin for Injection13 • Risk ratio for patients with stable disease: 0.470 (P<0.001 vs nonresponders) • Risk ratio for patients with partial response: 0.536 (P<0.031 vs nonresponders) In the absence of tumor progression, a minimum of 4 courses (approximately 3 months of therapy) is recommended because tumor response may be delayed14 • Median time to response was 9 to 12 weeks9,10,12,14 Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Please see accompanying full Prescribing Information, including BOXED WARNING. Keep all her options open

Proven single agent

Hycamtin for Injection consistently provided significant clinical benefit in 6 key trials6,8-12

CHOOSE

Hycamtin for Injection

AS FIRST SINGLE AGENT FOR RELAPSED OVARIAN CANCER

In the treatment of relapsed ovarian cancer

Regardless of Sensitivity, Hycamtin for Injection Was Proven Effective When Used in Relapsed Ovarian Cancer Hycamtin for Injection demonstrated significant response rates in patients with relapsed, platinum-sensitive disease in 4 key trials6,8,10,12 Overview of Clinical Trials With Hycamtin for Injection in Relapsed, Platinum-Sensitive Ovarian Cancer Overall response OVERALL DISEASE RESPONSE (%)

40

32.6% 30

28.8%

26.7%

28.8%

20

10

0

MCGUIRE8 (n=46)

TEN BOKKEL HUININK10 (n=52)

CREEMERS12 (n=30)

GORDON6 (n=111)

Hycamtin for Injection provided a significant response duration in patients with relapsed, platinum-sensitive disease8 Median time-to-event parameters and median survival in an open-label trial of Hycamtin for Injection (McGuire) in patients with primary, relapsed, platinum-sensitive disease (n=46)8 Median Time to Response

6

10 WEEKS

Median Response DURATION

44.8 WEEKS

Median PROGRESSIONFREE Response

38.4 WEEKS

The use of Hycamtin for Injection after relapse allows clinicians to reserve agent(s) used in initial therapy, other single agents, and doublets for subsequent relapses.2

Hycamtin for Injection has been proven effective in relapsed, platinum-resistant/refractory disease in 5 key trials6,9-12 Overview of Clinical Trials With Hycamtin for Injection in Relapsed Platinum-Resistant/Refractory* Ovarian Cancer Author

Number of Patients

Overall Disease Response†

Stable Disease‡

Clinical Benefit§

Median TTP

Median Survival¶

124#

6.5%

42.7%

49.2%

N/A

41.3

Bookman9

113#

12.4%

27.4%

39.8%

N/A

N/A

ten Bokkel Huinink10

60#

13.3%

N/A

N/A

N/A

N/A

Kudelka11

30#

13.3%

56.7%

70.0%

N/A

40.0

Creemers12

62

11.2%

22.3%

33.5%

9.9

N/A

Hycamtin for Injection achieved significant responses in 5 key trials6,9-12 OVERALL Disease Response

7%-13%

Stable disease

23%-57%

clinical benefit

34%-70%

* Platinum-resistant/refractory disease is defined as disease that has progressed on primary therapy or after a treatment-free interval of <6 months. † Response rates (partial response, complete response, and stable disease) independently confirmed. ‡ Stable disease was defined as any measurement that did not fulfill the criteria of response or progression and lasted at least 8 weeks.

(NOTE: Kudelka study defined stable disease as “a steady state or <partial response with no disease progression for at least 3 weeks.”) § Clinical benefit=response rate + stable disease.  TTP=time to progression (weeks). ¶ Weeks. # Intent-to-treat population.

N/A=not assessed.

Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Please see accompanying full Prescribing Information, including BOXED WARNING. Keep all her options open

efficacy across sensitivities

Gordon6

CHOOSE

AS FIRST SINGLE AGENT FOR RELAPSED OVARIAN CANCER

Hycamtin for Injection

In the treatment of RELAPSED ovarian cancer

Hycamtin for Injection and Progression-Free Survival— a Comparison of Approved Single Agents When compared with Doxil®* (doxorubicin HCI liposome injection), Hycamtin for Injection showed clinically similar outcomes6 • In the Gordon et al study, patients treated with Hycamtin for Injection or Doxil showed similar outcomes in the primary efficacy end point of progression-free survival6

Median progression-free survival6 Hycamtin for Injection

17.0 weeks

DOXIL

16.1 weeks

Secondary end points from Gordon et al6 Treatment Response for the Intent-to-Treat Population Hycamtin for Injection (N=235)

Doxil (N=239)

50

40.4%

PATIENTS (%)

40

32.2% 30 20

17.0%

19.7%

10 0

4.7% OVERALL RESPONSE RATE

*Doxil is a registered trademark of ALZA Corporation.

8

12.3%

15.9%

3.8%

COMPLETE RESPONSE RATE

PARTIAL RESPONSE RATE

STABLE DISEASE

Use Hycamtin for Injection after relapse for optimal safety and tolerability. Cumulative toxicities associated with other therapies are minimized when Hycamtin for Injection is sequenced correctly.2

Hematologic Side Effects With Hycamtin for Injection Are Predictable and Manageable and Neutropenia Is Noncumulative Over Time The most common grade 3/4 hematologic adverse events occurring in patients treated with either Hycamtin for Injection or paclitaxel were14: • Grade 4 neutropenia (80% vs 21%) • Grade 3/4 anemia (41% vs 6%) • Grade 4 thrombocytopenia (27% vs 3%) • Documented sepsis (5% vs 2%)

With appropriate management, median neutrophil nadirs did not worsen upon continued therapy15 After the first cycle, patients may have received G-CSF or reduced doses of Hycamtin for Injection; some patients may have discontinued Hycamtin for Injection due to myelosuppression. Every subsequent cycle included patients with grade 4 hematologic toxicity. ‡ Number in parentheses is the number of patients with lab data available at each cycle.

The lowest neutrophil nadir occurred during course 1 of therapy. Subsequent use of G-CSF and dose reductions and early withdrawals account for higher nadir values after course 1.

There was no evidence of cumulative toxicity with subsequent courses of therapy with Hycamtin for Injection. †

NEUTROPHIL COUNT (10 9 CELLS/L)

Median Neutrophil Nadirs by Cycle† (n=879) in Patients Receiving Hycamtin for Injection (Combined Ovarian Cancer and Small Cell Lung Cancer Studies) 0.9 (560)

0.7

(73)

(175)

(353)

0.5

(97)

(478)

0.6

0.4

(144)

(304)

0.8

(739) (859)

‡

0.3 0.2 1

2

3

4

5

6

7

8

9

10

CYCLES DELIVERED

safEty/tolerability

Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Please see accompanying full Prescribing Information, including BOXED WARNING.

Keep all her options open

CHOOSE

AS FIRST SINGLE AGENT FOR RELAPSED OVARIAN CANCER

Hycamtin for Injection

Hematologic Side Effects With Hycamtin for Injection Are Predictable and Manageable and Neutropenia Is Noncumulative Over Time With appropriate management, median platelet nadirs did not worsen upon continued therapy15 Median Platelet Nadirs by Cycle* (n=879) in Patients Receiving Hycamtin for Injection (Combined Ovarian Cancer and Small Cell Lung Cancer Studies)

PLATELET COUNT (10 9 CELLS/L)

110 100

(563)

90

(482)

(747)

(356)

80

(145)

(305)

(73)

(176)

(97)

70 60

(862)†

50 40 30 0

1

2

3

4

5

6

7

8

9

10

CYCLES DELIVERED

* After the first cycle, patients may have received G-CSF or reduced doses of Hycamtin for Injection; some patients may have discontinued Hycamtin for Injection due to myelosuppression. Every subsequent cycle included patients with grade 4 hematologic toxicity. † Number in parentheses is the number of patients with lab data available at each cycle.

Median platelet nadir was 59 x 109/L for course 1, without evidence of cumulative toxicity of Hycamtin for Injection with subsequent courses; median nadir ranged from 86 to 95 x 109/L in courses 2 through 10. Platelet transfusions were administered in 4.4% of courses of Hycamtin for Injection.

After 4 treatment cycles, median hemoglobin nadirs stabilized15 Median Hemoglobin Nadirs by Cycle‡ (n=879) in Patients Receiving Hycamtin for Injection (Combined Ovarian Cancer and Small Cell Lung Cancer Studies) 100

(862)§

HEMOGLOBIN (g/L)

98 96 94

(145)

(305)

92

(356)

(747)

90

(563)

(73)

(176) (97)

(482)

88 86 84

1

2

3

4

5

6

CYCLES DELIVERED

10

7

8

9

10

‡ After the first cycle, patients

may have received G-CSF or reduced doses of Hycamtin for Injection; some patients may have discontinued Hycamtin for Injection due to myelosuppression. Every subsequent cycle included patients with grade 4 hematologic toxicity. § Number in parentheses is the number of patients with lab data available at each cycle.

Median hemoglobin nadir was relatively stable for courses 1 through 10 of therapy with Hycamtin for Injection, with no clear evidence of cumulative toxicity. The median percent decrease from baseline was slightly higher (22% to 27% compared with 18%) after course 1.

Use Hycamtin for Injection after relapse for manageable safety and tolerability. Cumulative toxicities associated with other therapies are minimized when Hycamtin for Injection is sequenced correctly.2

Dose Adjustments for Patients With Renal Impairment

14

• I nitial dose of Hycamtin for Injection should be adjusted based on creatinine clearance —No dosage adjustments appear to be required in patients with mild renal impairment; dosage adjustment is recommended for patients with moderate renal impairment14 — Creatinine clearance–based dosing may minimize myelosuppression16

Dosage recommendations for patients with renal impairment

Mild

No dosage adjustment required

Moderate

Dosage adjustment to 0.75 mg/m2

Severe

Insufficient data available

Renal impairment defined by creatinine clearance: mild (CLcr 40-60 mL/min); moderate (CLcr 20-39 mL/min).

Using the Right Treatment at the Right Time Can Help You Better Manage Toxicity • Nonplatinum agents are more effective and less toxic when used at first relapse2,9 — Administration of Hycamtin for Injection to patients with multiple prior therapies may require dose reductions because of diminished bone marrow reserves or renal impairment2 • Cumulative toxicities may require termination of the treatment with other single agents, even when the patient still exhibits a positive response17

Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Please see accompanying full Prescribing Information, including BOXED WARNING. Keep all her options open

In Clinical Studies, Most Nonhematologic Side Effects Are Generally Mild and Manageable Mild to moderate, nonhematologic side-effect profile with Hycamtin for Injection10,14 •T he most frequently reported nonhematologic side effects were nausea, vomiting, fatigue, sepsis with neutropenia, constipation, diarrhea, and asthenia14 •S ide effects occurring with Hycamtin for Injection were not dose limiting, and severe diarrhea was rare10 •P remedications were not routinely used in clinical studies14 Summary of Nonhematologic Side Effects Occurring With Hycamtin for Injection by Number of Patients (n=879) and Courses (n=4124) Adverse Event

Gastrointestinal Nausea Vomiting Diarrhea Constipation Abdominal pain Stomatitis Anorexia Other Side Effects Fatigue Fever Pain* Asthenia Rash† Dyspnea Coughing Headache

Grade 3

Grade 4

% patients

% courses

% patients

% courses

7 4 3 2 2 1 2

2 1 1 1 1 <1 1

1 1 1 1 2 <1 <1

<1 <1 <1 <1 <1 <1 <1

5 1 2 4 1 5 1 1

2 <1 1 1 <1 2 <1 <1

0 <1 1 2 0 3 0 <1

0 <1 <1 <1 0 1 0 0

*Includes body pain, back pain, and skeletal pain. † Includes pruritis, rash erythematous, urticaria, dermatitis, bulleous eruption, and maculopapular rash.

References: 1. Markman M, Rothman R, Hakes T, et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.

J Clin Oncol. 1991;9:389-393. 2. Armstrong DK. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist. 2002; 7(suppl 5):20-28. 3. Gore ME, Fryatt I, Wiltshaw E, Dawson T. Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecol Oncol. 1990;36:207-211. 4. Dunton CJ. Management of treatment-related toxicity in advanced ovarian cancer. Oncologist. 2002;7(suppl 5):11-19. 5. Bookman MA. Extending the platinum-free interval in recurrent ovarian cancer: the role of topotecan in second-line chemotherapy. Oncologist. 1999;4:87-94. 6. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19:3312-3322. 7. Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30–49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gyncol Oncol. 2004;95:1-8. 8. McGuire WP, Blessing JA, Bookman MA, Lentz SS, Dunton CJ. Topotecan has substantial antitumor activity as first-line salvage therapy in platinum-sensitive epithelial ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2000;18:1062-1067. 9. Bookman MA, Malmström H, Bolis G, et al. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol. 1998;16:3345-3352. 10. ten Bokkel Huinink W, Gore M, Carmichael J, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997;15:2183-2193. 11. Kudelka AP, Tresukosol D, Edwards CL, et al. Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma. J Clin Oncol. 1996;14:1552-1557. 12. Creemers GJ, Bolis G, Gore M, et al. Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study. J Clin Oncol.

1996;14:3056-3061. 13. Cesano A, Lane SR, Poulin R, Ross G, Fields SZ. Stabilization of disease as a useful predictor of survival following second-line chemotherapy in small cell lung cancer and ovarian cancer patients. Int J Oncol. 1999;15:1233-1238. 14. Hycamtin (topotecan HCl) for Injection Prescribing Information. 15. Data on file, GlaxoSmithKline. 16. O’Reilly S, Rowinsky EK, Slichenmyer W, et al. Phase I and pharmacologic study of topotecan in patients with impaired renal function. J Clin Oncol. 1996;14(12):3062-3073. 17. Doxil (doxorubicin HCl liposome injection) for intravenous infusion Prescribing Information. Raritan, NJ: Ortho Biotech Products, LP; June 2008.

12

Important Safety Information

14

Indication Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

WARNING Hycamtin (topotecan HCl) for Injection should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. Therapy with Hycamtin for Injection should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection and death, frequent peripheral blood cell counts should be performed on all patients receiving Hycamtin for Injection.

Contraindications Hycamtin for Injection is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or to any of its ingredients. Hycamtin for Injection should not be used in patients who are pregnant or breastfeeding, or those with severe bone marrow depression.

Warnings Bone marrow suppression (primarily neutropenia) is the dose-limiting toxicity of Hycamtin for Injection. Neutropenia is not cumulative over time. The following data on myelosuppression is based on the combined experience of 879 patients with metastatic ovarian cancer or small cell lung cancer treated with Hycamtin for Injection monotherapy at a dose of 1.5 mg/m2/day x 5 days and the experience of 140 patients with cervical cancer randomized to receive Hycamtin for Injection 0.75 mg/m2/day on days 1, 2, and 3 plus cisplatin 50 mg/m2 on day 1. Neutropenia: Ovarian and small cell lung cancer experience grade 4 neutropenia (<500 cells/mm3) was most common during course 1 of treatment (60% of patients) and occurred in 39% of all courses, with a median duration of 7 days. The nadir neutrophil count occurred at a median of 12 days. Therapy-related sepsis or febrile neutropenia occurred in 23% of patients, and sepsis was fatal in 1%. Pancytopenia has been reported. Topotecan-induced neutropenia can lead to neutropenic colitis.

Fatalities due to neutropenic colitis have been reported in clinical trials with Hycamtin for Injection. In patients presenting with fever, neutropenia, and a compatible pattern of abdominal pain, the possibility of neutropenic colitis should be considered. Thrombocytopenia: Ovarian and small cell lung cancer experience grade 4 thrombocytopenia (<25,000/mm3) occurred in 27% of patients and in 9% of courses, with a median duration of 5 days and platelet nadir at a median of 15 days. Platelet transfusions were given to 15% of patients in 4% of courses. Anemia: Ovarian and small cell lung cancer experience grade 3/4 anemia (<8 g/dL) occurred in 37% of patients and in 14% of courses. Median nadir was at day 15. Transfusions were needed in 52% of patients in 22% of courses. In ovarian cancer, the overall treatment-related death rate was 1%.

Hycamtin for Injection should be administered only in patients with adequate bone marrow reserves, including a baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3. Frequent monitoring of peripheral blood cell counts should be instituted during treatment with Hycamtin for Injection.

Patients should not be treated with subsequent courses of Hycamtin for Injection until neutrophils recover to >1,000 cells/mm3, platelets recover to >100,000 cells/mm3, and hemoglobin levels recover to 9.0 g/dL (with transfusion if necessary). Severe myelotoxicity has been reported when 5-day dosing of Hycamtin for Injection is used in combination with cisplatin.

Hycamtin for Injection may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Hycamtin for Injection.

Drug Interactions Concomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, it should not be initiated until 24 hours after completion of treatment with Hycamtin for Injection.

Myelosuppression was more severe when Hycamtin for Injection, at a dose of 1.25 mg/m2/day x 5 days, was given in combination with cisplatin at a dose of 50 mg/m2 in phase I studies. In one study, 1 of 3 patients had severe neutropenia for 12 days, and a second patient died with neutropenic sepsis.

Adverse Events The most common serious adverse event is myelosuppression.

Severe neutropenia, the dose-limiting toxicity for Hycamtin for Injection, occurred in 78% of 879 ovarian and small cell lung cancer patients treated. Other hematologic adverse events reported include severe leukopenia (32%), severe thrombocytopenia (27%), and severe anemia (37%).

Frequently reported nonhematologic adverse events associated with use of Hycamtin for Injection included nausea (64%), vomiting (45%), diarrhea (32%), alopecia (49%), fatigue (29%), and dyspnea (22%).

Most nonhematologic toxicities were grade 1 or 2.

Keep all her options open

CHOOSE

Hycamtin for Injection

AS FIRST SINGLE AGENT FOR RELAPSED OVARIAN CANCER

Treat With Single-Agent Hycamtin for Injection to...

Maximize efficacy • Extending patients’ platinum-free interval by using a nonplatinum agent increases the probability of response to platinum reinduction at the next relapse1,2 • With more than a decade of clinical experience and clinical trials data, Hycamtin for Injection has been proven effective in relapsed ovarian cancer 6,8-12 • Hycamtin for Injection has more than a decade of clinical experience and is 1 of the most proven single agents in relapsed ovarian cancer 6-12

Overview of efficacy with Hycamtin for Injection in relapsed ovarian cancer 6-12 OVERALL DIsease Response*

13.3%-32.6%

Stable disease†

20.7%-56.6%

clinical benefit‡

37.0%-80.4%

Minimize toxicity • The development of cumulative toxicities may decrease options for future chemotherapy treatment4 • Neutropenia with Hycamtin for Injection is noncumulative over time10,14

*Responses (partial response, complete response, and stable disease) independently confirmed. † Stable disease was defined as any measurement that did not fulfill the criteria of response or progression and lasted at least 8 weeks.

(NOTE: Kudelka study defined stable disease as “a steady state or <partial response with no disease progression for at least 3 weeks.”) ‡ Clinical benefit=overall response rate + stable disease.

Hycamtin for Injection is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Please see accompanying full Prescribing Information, including BOXED WARNING.

©2008 The GlaxoSmithKline Group of Companies All rights reserved. Printed in USA. HYC483R0 September 2008

Keep all her options open