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01 Leonard Treatment decisions.333333ppt
- 1. Key factors fortreatment decision making Bob Leonard South West Wales Cancer Institute Swansea, UK
- 2. Major drivers Tumourbiology Patient characteristics Prior therapy
- 3. Biology drives treatmentchoices in metastatic breast cancer (MBC) Local Metastatic Negative Positive ER/PgR HER2 Negative Positive Bone/soft tissue Visceral
- 4. HER2/ER status Tested? Problems with rapid access to result if not previously tested?
- 5. Patient characteristics influence treatmentdecisions Age Performance status Patient history Patient preference Comorbidities e.g. diabetes, impaired cardiac function Sites Pace of relapse Previous therapy Fitness Cardiac function Renal/hepatic function
- 6. Prior therapy drives treatmentdecisions
- 7. Prior therapy: adjuvantsetting Anthracyclines – dose: cumulative risk of CHF, decreased LVEF – which anthracycline was used? – tolerability; hair loss Taxoids – which taxoid was used? Time to relapse – Sledge data (AT versus A T): relapse 2 years significant independent negative prognostic factor¹ Hormonal therapy – relapse whilst on hormonal therapy? ¹Sledge GW, et al. J Clin Oncol 2003;21:588–92 CHF = congestive heart failure LVEF = left ventricular ejection fraction
- 8. After relapse Anthracyclinesagain? – toxicity and cardiac damage Taxoids – myelotoxic, clinical toxicity Drug resistance – especially early relapse
- 9. Oral Xeloda: the keystoneof MBC treatment Unique tumour specific mechanism of action via higher intratumoural thymidine phosphorylase In previously treated BC – consistently high single-agent activity – in combination with Taxotere, only cytotoxic agent to extend survival in MBC – favourable safety with no cumulative toxicity; minimal myelosuppression and alopecia Provides convenient oral therapy that patients prefer1 1 Liu G, et al. J Clin Oncol 1997;15:425–32
Editor's Notes
- #2 At the present time, the main factors driving treatment choices in breast cancer include: Tumour biology: accurate tumour evaluation according to clinical and pathological criteria ensures that patients can be offered suitable treatments at the appropriate stage of their disease surgery radiotherapy hormone treatment chemotherapy, with and without trastuzumab (Herceptin). Patient characteristics Older, frail patients may be less able to tolerate intensive chemotherapies than fit, young patients with good performance status. Comorbidities may mean a patient is less suited to intensive chemotherapy. Prior treatment If a patient relapses >2 years after first response to treatment, they may respond positively to that treatment again. However, a shorter relapse time usually indicates that a change in therapeutic approach is required. A lack of response to a prior chemotherapy will also require a change in treatment choice. The cumulative dose of certain treatments, such as anthracyclines, may preclude further treatment with agents of the same class.
- #3 Receptor status is an extremely important parameter influencing the treatment of breast cancer positive ER/PgR receptor status means that a patient is more likely to respond to hormone therapy, even in the event of a recurrence negative ER/PgR receptor status means that a patient will not respond to hormone therapy, and chemotherapy must be considered if a patient is HER2 positive, they are suitable for treatment with trastuzumab. Local disease can be best treated with lumpectomy, mastectomy or radiation. For metastatic disease, systemic chemotherapy is the most appropriate treatment there are a number of treatment options, the choice of which is influenced by disease characteristics, including location and number of metastatic sites.
- #4 When choosing a treatment the physician must first determine whether the patient has been, or needs to be, tested for her HER2 and ER status. Testing may lead to delays in starting treatment as there can be problems with rapid access to the result if a patient has not previously been tested.
- #5 Patient needs and characteristics (age, performance status, comorbidities, personal circumstances and preferences) must be considered when deciding which treatment should be administered patients with good performance scores and rapidly progressing disease with visceral metastases may derive most benefit from intensive, combination therapies older patients with more indolent disease could be more suited to a gentler approach with single-agent chemotherapy.
- #7 Currently, anthracyclines are among the most commonly used agents in the adjuvant setting: however, anthracyclines are associated with both acute and chronic cardiac toxicity most commonly, acute toxicities include myelosuppression; anthracycline combinations may also be associated with a high incidence of total alopecia [1] the risk of cardiac complications, such as life-threatening congestive heart failure (occurring in 10–15% of patients), is increased with exposure to cumulative anthracycline doses of more than 600mg/m2 [2]. Taxoids are becoming more commonly used in the adjuvant setting: in a large phase III trial, disease-free survival (DFS) was significantly prolonged with TAC (5-year DFS 75%) versus FAC (5-year DFS 68%), and patients receiving TAC were 30% less likely to die compared with those receiving FAC, but benefits were offset by increased toxicity [3] docetaxel is generally considered to be a more effective agent than paclitaxel: the TAX311 randomised, phase III trial compared docetaxel (100mg/m2) with paclitaxel (175mg/m2) [4] docetaxel significantly improved time to progression (TTP) (5.7 vs 3.6 months for paclitaxel, p=0.0001) and overall survival (15.4 vs 12.7 months for paclitaxel, p=0.03), although response rates were similar (32 vs 25% for paclitaxel, p=0.10). Interestingly, a recent study in the metastatic setting showed that reduction in docetaxel dose from 75mg/m2 to 5560mg/m2 may not compromise efficacy [5] TTP was 13 and 15 weeks with the 60 and 75mg/m2 doses, respectively, with overall survival similar in the two arms (11 and 10 months with the 60 and 75mg/m2 doses, respectively) in the same study, docetaxel 100mg/m2 was associated with significantly more grade 3/4 adverse events (febrile neutropenia: 14% with docetaxel 100mg/m2 versus 7% and 5% with 75mg/m2 60mg/m2, respectively). Data show that in patients receiving doxorubicin followed by paclitaxel, those patients who relapsed within 2 years of adjuvant anthracyclines had a poor prognosis compared with those who were disease-free for longer than 2 years [6]. Hormonal therapy, with oral agents such as tamoxifen, is well tolerated, but not suited to patients with ER/PR negative disease [7] refractory tumours or those developing resistance to tamoxifen may be responsive to third-generation, non-steroidal aromatase inhibitors such as anastrazole, letrozole and vorozole, or the steroidal inhibitor exemestane chemotherapy may be indicated in patients who have relapsed on several hormonal therapies. 1. Joensuu H et al. J Clin Oncol 1998;16:3720–30. 2. Wojtacki J et al. Med Sci Monit 2000;6:411–20. 3. Martin M et al. Breast Cancer Res Treat 2003; (Abst 43). 4. Jones S et al. Breast Cancer Res Treat 2003; 82 (Suppl 1):S9–10. 5. Mouridsen H et al. Breast Cancer Res Treat 2002;76(Suppl. 1):S88 (Abst 327). 6. Sledge GW et al. J Clin Oncol 2003;21:588–92. 7. Reddy P et al. Am J Health Syst Pharm. 2000;57:1315–22; 1323–5.
- #8 After relapsing on adjuvant anthracyclines, patients could receive Further anthracyclines, although the level of toxicity experienced plus the risk of cardiac damage that can occur with anthracyclines must be considered. Taxoids, but these are associated with a high incidence of myelosuppression and clinical toxicities that need to be taken into account. The physician and patient together must also consider the possibility of drug resistance, especially if relapse was early.
- #9 Based on the large body of evidence from clinical trials, Xeloda has become an essential component of treatment for metastatic breast cancer (MBC). A phase III trial in anthracycline-pretreated patients demonstrated that the addition of Xeloda to Taxotere (XT) resulted in significantly superior time to disease progression, response rates, and overall survival [1]. XT is the only cytotoxic combination to extend survival beyond that achieved with Taxotere. Single-agent Xeloda is also highly effective, comparing favorably to paclitaxel and CMF in the first- and second-line treatment of MBC [2,3]. In patients with taxane-pretreated MBC, Xeloda produces consistently impressive response rates and overall survival of approximately 1 year [4–8]. Offering the convenience of an oral agent, Xeloda achieves high activity with a favorable safety profile minimal myelosuppression minimal alopecia. The high activity and favourable safety of Xeloda-based therapy in the metastatic setting have provided a strong rationale for ongoing/planned evaluation in the (neo)adjuvant setting. 1. O’Shaughnessy J et al. J Clin Oncol 2002;20:2812–23. 2. Talbot D, et al. Br J Cancer 2002;86:1367–72. 3. O'Shaughnessy J et al. Ann Oncol 2001;12:1247–54. 4. Blum JL et al. Eur J Cancer 2001;37(Suppl. 6):S190 (Abst 693). 5. Blum JL et al. Cancer 2001;92:1759–68. 6. Reichardt P et al. Ann Oncol 2003;14:1227–33. 7. Fumoleau P et al. Eur J Cancer 2003;In press. 8. Maung K. Clin Breast Cancer 2003;3:375–7.