Abstract
Context
Objective
Evidence acquisition
Evidence synthesis
Conclusions
Keywords
1. Introduction
2. Evidence acquisition
3. Evidence synthesis
3.1 Prostate cancer
3.1.1 Risk factors and treatment of patients with minimal pain
- •Most delegates (51%) identified PSADT as the primary risk factor for assessing the patient's 1-yr survival probability. The faculty, however, noted that although pretreatment PSADT can predict overall survival, it cannot be used to predict the risk of death within 1 yr and requires considerable time to determine. Alkaline phosphatase levels (chosen by 2% of delegates) are important in the TAX 327 nomogram; they provide a good prognostic variable for disease extent and are particularly predictive of bone metastases. The presence of new bone metastases (9%), pain (17%), and visceral disease (12%) are also considered predictive of survival; however, the latter two variables were not present in the case history of this patient.
- •Sixty percent of delegates chose to treat this patient by secondary hormonal manipulation; the remainder chose to initiate docetaxel treatment. The faculty noted that secondary hormonal manipulation has not been shown to affect overall survival, and there may be insufficient time for hormonal manipulation if a patient is rapidly progressing. Disease aggressiveness may be underestimated in patients with minimal pain.
Prognostic factors | CALGB | MSKCC | TAX 327 |
---|---|---|---|
PSA | X | X | X |
Alkaline phosphatase | – | X | X |
Haemoglobin | X | X | X |
Performance status | ECOG | Karnofsky | Karnofsky |
LDH | X | X | – |
Gleason score | X | – | WHO |
Presence of visceral disease | X | – | – |
Age | – | – | X |
Albumin | – | X | – |
Treatment with docetaxel | – | – | X |
Liver metastases | – | – | X |
Pain at baseline | – | – | X |
PSADT | – | – | X |
Metastatic site | – | – | X |
Type of progression | – | – | X |
3.1.2 Senior adult population: Addressing the right treatment approach
SEER stat fact sheets. National Cancer Institute Surveillance Epidemiology and End Results Web page. http://seer.cancer.gov/statfacts/html/prost.html. Accessed April 30, 2009.
Droz J, Sternberg C, Balducci L, et al. International Society of Geriatric Oncology (SIOG) prostate cancer guidelines proposal in senior adult men [abstract 253]. American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium; February 14-16, 2008; San Francisco, CA. http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=54&abstractID=20410. Accessed April 30, 2009.
- •The MMSE is a valuable and quick cognitive screening tool for determining whether more in-depth testing is needed; low scores may result from depression, dementia, or delirium due to pain medication. Importantly, a low score may affect treatment compliance, and patients should be referred to a psychiatrist to determine the cause of a low score, although this referral should not delay treatment initiation. Proactive multidisciplinary supportive care to identify, monitor, and address the health status of senior adults is critical to successful management.
- •The majority of delegates (84%) chose to treat this patient with docetaxel (75 mg/m2) every 3 wk (Fig. 1). The remaining delegates chose to treat the patient with best supportive care (9%), strontium (5%), or prednisone (2%). The faculty noted that there is no evidence to support weekly docetaxel treatment on the basis of difference in toxicity compared to the every-3-wk regimen. Furthermore, weekly docetaxel (30 mg/m2) did not significantly improve survival compared with mitoxantrone in the TAX 327 study.Fig. 1Delegates’ response to the question: What treatment approach would you proceed with?
3.1.3 Retreatment of advanced prostate cancer: When and whom to consider?
- Berthold D.R.
- Pond G.R.
- Roessner M.
- de Wit R.
- Eisenberger M.
- Tannock A.I.
Eymard J, Oudard S, Gravis G, et al. Second-line chemotherapy with docetaxel (D) in men treated with docetaxel-based regimen for metastatic hormone-refractory prostate cancer (mHRPC) [abstract 249]. American Society of Clinical Oncology 2007 Prostate Cancer Symposium. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=46&abstractID=20375. Accessed April 30, 2009.
- •The majority of delegates (81%) identified previous docetaxel response as the primary factor for assessing the patient's disease severity and future treatment (Fig. 2). The remaining delegates chose the extent of pain (13%) or PSA level (6%).Fig. 2Delegates’ response to the question: What primary factor would you consider to assess the patient's severity of disease and future treatment?
- •There was 100% consensus among delegates that the patient should be retreated with docetaxel. The faculty noted that the efficacy of docetaxel has been demonstrated using 10 cycles in the TAX 327 study and that there is no evidence that fewer cycles will produce the same overall survival benefit.
3.2 Renal cell carcinoma: What is on the horizon and beyond?
- •The majority of delegates (87%) would have chosen to enrol him in a clinical study with a targeted therapy. The remaining delegates would have proceeded with high-dose IFN α (10%), IFN α and IL-2 (2%), or best supportive care (1%).
- •At this point, 98% of delegates chose to treat the patient with a targeted agent (extended-access programme with sunitinib). The remainder chose best supportive care.
Agent | Setting | Progression-free survival |
---|---|---|
Sunitinib (VEGF and PDGF receptor tyrosine kinase inhibitor) | Untreated | 11 mo compared with 5 mo for IFN α [38] |
Sorafenib (VEGF and PDGF receptor tyrosine kinase inhibitor) | Refractory to cytokine-based therapy | 5.5 mo compared with 2.8 mo for placebo in cytokine-refractory patients [34] |
Bevacizumab (Monoclonal antibody to VEGF) | Untreated | 10.2 mo in combination with IFN α months compared with 5.4 mo for IFN α alone [35] |
Temsirolimus (mTOR inhibitor) | Untreated (poor prognosis) | 3.8 mo compared with 1.9 mo for IFN α [36] ; median overall survival was 10.9 mo compared with 7.3 mo for IFN α |
Everolimus (mTOR inhibitor) | Refractory to sunitinib, sorafenib, or both | 4.0 mo compared with 1.9 mo for placebo [37] |
Setting | Patients | Therapy (level 1) | Other options (level 2 or higher) |
---|---|---|---|
Untreated | Good or intermediate risk | Sunitinib | High-dose IL-2 |
Bevacizumab and IFN α | Sorefanib | ||
Clinical trial | |||
Observation | |||
Poor risk | Temsirolimus | Sunitinib | |
Clinical trial | |||
Refractory | Cytokine | Sorafenib | Sunitinib |
Bevacizumab and IFN α | |||
VEGF–TKI | Everolimus | Clinical trial | |
mTOR | Clinical trial |
3.3 Advanced bladder cancer: Past, present, and future chemotherapy regimens
- Sternberg C.N.
- de Mulder P.H.
- Schornagel J.H.
- et al.
Bellmunt H, von der Masse H, Mead GM, et al. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy; EORTC30987/Intergroup Study [ASCO abstract 5030]. J Clin Oncol 2007;25:p242s.
Bellmunt J, von der Maase H, Theodore C, et al. Randomised phase III trial of vinflunine (V) plus best supportive care (B) vs B alone as 2nd line therapy after a platinum-containing regimen in advanced transitional cell carcinoma of the urothelium (TCCU) [ASCO abstract 5028]. J Clin Oncol 2008;26:p257s.
- •The majority of delegates (65%) chose to proceed with intravesical bacillus Calmette-Guérin (BCG) immunotherapy. The remaining delegates chose to repeat TURB (22%) or to perform a radical cystectomy (13%).
- •At this point, 97% of delegates chose to perform a radical cystectomy. The remainder chose to repeat TURB (2%) or to perform a partial cystectomy (1%).
- •At this point, 53% of delegates chose to proceed with GC chemotherapy, 18% with gemcitabine and paclitaxel chemotherapy, 19% with radiotherapy, and 10% with M-VAC.
- •The majority of delegates chose to proceed with consolidative radiotherapy (64%). The remainder chose to enrol the patient in a clinical trial (16%) or to proceed with GC chemotherapy (20%).
4. Conclusions
- •Docetaxel administered at 75 mg/m2 every 3 wk provides significant benefits in mCRPC patients, regardless of age and pain.
- •Treatment decisions for senior adults should be based on patient health status rather than on chronologic age.
- •Asymptomatic mCRPC patients with adverse prognostic factors are candidates for chemotherapy.
- •Retreatment with docetaxel at relapse may be a therapeutic option for mCRPC patients who responded well to first-line docetaxel treatment.
- •Targeted agents have demonstrated increases in overall survival and progression-free survival in first- and second-line treatment, respectively, of RCC.
- •Clinical trials investigating targeted therapies in bladder cancer are finally under way.
Conflicts of interest
Funding support
Acknowledgements
References
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