Abstract
PURPOSE
Prior noncontemporary studies showed that oral cyclophosphamide is an active treatment of metastatic castration-resistant prostate cancer (mCRPC). However, cyclophosphamide is currently underutilized in routine clinical practice given the lack of survival benefit and the emergence of more effective treatments.
METHODS
We retrospectively reviewed our institutional database to identify patients with mCRPC treated with cyclophosphamide. Prostate-specific antigen decrease ≥50% from baseline (PSA50) response was determined as the proportion of patients achieving a prostate-specific antigen (PSA) decline ≥50% from baseline. Radiographic responses and progression were evaluated by Prostate Cancer Working Group 3. Survival estimates used the Kaplan-Meier method, and correlations were made with Chi-square test for categorical variables.
RESULTS
From January 2011 to January 2023, 341 patients with mCRPC received oral cyclophosphamide at a tertiary cancer center in São Paulo, Brazil. The most common regimen (95%) was 100 mg once daily 21 days on, 7 days off. At prostate cancer diagnosis, the median age was 64.4 years (IQR, 59.4-70.8), 61.9% had metastatic de novo disease, and 55.5% had Gleason ≥8. The median number of previous treatment lines was three (IQR, 2-4). Any PSA decline was observed in 33.4%, and 13.2% had a PSA50 response. Median response duration was 2.1 months (IQR, 1.4-3.8). Ten patients (3%) were treated for ≥1 year. PSA50 response was associated with no prior docetaxel use and Eastern Cooperative Oncology Group performance status 0 or 1.
CONCLUSION
Oral cyclophosphamide is a feasible treatment option for patients with mCRPC, particularly in a scenario of limited health care resources.
INTRODUCTION
Prostate cancer is a major public health concern, with an estimated 1.4 million new patient cases reported globally in 2020.1 When metastatic disease progresses to a castration-resistant state, the 5-year relative survival has been reported to be as low as 30%.2 However, the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has dramatically changed over the past 20 years.
CONTEXT
Key Objective
Is oral cyclophosphamide a treatment option for advanced metastatic castration-resistant prostate cancer (mCRPC), particularly in resource-limited settings?
Knowledge Generated
Oral cyclophosphamide has antitumor activity in a small subgroup of patients, but may improve symptoms and some patients experience durable responses, with limited toxicity.
Relevance
Oral cyclophosphamide may be considered in the treatment landscape of advanced mCRPC in later lines of therapy, particularly in scenarios of limited health care resources.
The introduction of new life-prolonging therapies, such as taxanes, antiandrogen receptor signaling inhibitors, radiopharmaceuticals, and targeted therapies, has significantly improved clinical outcomes.3-10 Despite these advances, the high financial burden associated with these treatments poses a significant challenge for patients and health care systems. Disparities in health care access and the costs of modern treatments are major obstacles to successfully treating patients with mCRPC, particularly in low- and middle-income countries.
Cyclophosphamide, an alkylating agent used in oncology since the late 1950s, has shown antiangiogenic and immunomodulatory effects in various tumors when administered orally in a low-dose metronomic regimen.11 The first evaluation of oral metronomic cyclophosphamide for mCRPC occurred in 1993, demonstrating a favorable safety profile and moderate clinical efficacy.12 Many subsequent prospective and retrospective studies have shown similar results, although often limited by small sample sizes. Additionally, no clinical or molecular predictors of cyclophosphamide efficacy in mCRPC have been identified to date.
Our hypothesis is that cyclophosphamide is a treatment option, with a favorable toxicity profile, particularly in limited-resource settings. In this study, we report the characteristics and outcomes from a large retrospective cohort of patients with mCRPC treated with oral metronomic cyclophosphamide at a public cancer center in São Paulo, Brazil. Potential prognostic or predictive factors were investigated and described.
METHODS
Study Design and Patients
We searched our institutional clinical database to identify patients with mCRPC who received oral metronomic cyclophosphamide. Data were extracted from electronic medical records, including demographics, pathological features, laboratorial data, treatment characteristics, and oncological outcomes. Approval from the local ethics committee was obtained before any study-related procedure (Accession Number: 1353/2018).
Eligible patients in the intention-to-treat analysis had a confirmed diagnosis of mCRPC and were treated with oral metronomic cyclophosphamide from January 2011 to January 2023. Patients provided a written informed consent unless in case of death, where the institutional review board waived the application of the consent form.
Exclusion criteria included cyclophosphamide usage for another concurrent neoplasm (except superficial skin cancer or low-grade non–muscle-invasive urothelial carcinoma) and patients with undetectable prostate-specific antigen (PSA). An exploratory analysis was conducted only with those who received more than consecutive 7 days of cyclophosphamide and with more than two PSA tests available (per-protocol population).
Outcomes and Statistical Considerations
The PSA levels before and during cyclophosphamide treatment were registered. Only values measured within 7 or less days before cyclophosphamide initiation were considered for this analysis. Prostate-specific antigen decrease ≥50% from baseline (PSA50) response was considered as the proportion of patients achieving a decrease of 50% or more from the baseline PSA level. The lowest PSA value during treatment was considered the best response. The patients who had less than two PSA tests available were considered as nonresponders. Overall survival (OS) was calculated from cyclophosphamide initiation until death or last follow-up visit. Time on treatment was calculated from cyclophosphamide initiation until treatment interruption or last follow-up visit. Baseline neutrophils, lymphocytes, eosinophils, and platelet counts were recorded if measured within 7 or less days before cyclophosphamide initiation and used to calculate neutrophil-to-lymphocyte, neutrophil-to-platelet, and eosinophil-to-platelet ratios.
The Kaplan-Meier method was used to estimate time-to-event variables. Log-rank test was used to compare survival estimates and Cox proportional hazard to determine effects on time-to-event variables. Univariate analysis was performed to identify factors associated with OS; factors with significant association (P < .05) in the univariate analysis were posteriorly tested in the multivariate model. The association between the PSA50 response and different factors was tested using the Chi-square test, and the calculated odds ratio was reported. Safety was analyzed considering the number and proportion of patients who required blood transfusions, had treatment suspended because of toxicities, and were hospitalized or died owing to adverse events. Statistical analysis was performed using R version 4.2.2 (2022-10-31). Significance was established as P < .05.
RESULTS
Patients and Disease Characteristics
From January 2011 to January 2023, 341 patients with mCRPC were treated with oral metronomic cyclophosphamide at our center (Fig 1). At prostate cancer diagnosis, the median age was 64.4 years (IQR, 59.4-70.8), 61.9% (n = 211) had de novo metastatic disease, and 13.2% (n = 45) had visceral metastasis. Patients who received oral cyclophosphamide were heavily pretreated, with a median number of previous treatment lines of three (IQR, 2-4), with 73.6% (n = 251) having received prior docetaxel (Table 1). At treatment initiation, 52.5% (n = 179) had Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1. The most common cyclophosphamide regimen used was 100 mg once daily 21 days on, 7 days off (n = 324, 95.0%). Five patients (1.5%) received 100 mg once daily 14 days on, 7 days off, and 12 patients (3.5%) received 50 mg once daily continuously.
FIG 1.
Description of patients with metastatic castration-resistant prostate cancer treated with oral metronomic cyclophosphamide. PSA, prostate-specific antigen.
TABLE 1.
Baseline Patient Characteristics
| Baseline characteristic | Value |
|---|---|
| Age, years, median (IQR) | 64.4 (59.4-70.8) |
| ECOG-PS, No. (%) | |
| 0-1 | 179 (52.5) |
| ≥2 | 162 (47.5) |
| Race, No. (%) | |
| White | 215 (63.0) |
| Black | 45 (13.2) |
| Multiracial | 70 (20.5) |
| Comorbidities, No. (%) | |
| Hypertension | 187 (54.8) |
| Diabetes mellitus | 63 (18.5) |
| Chronic kidney disease | 23 (6.7) |
| Myocardial infarction | 21 (6.2) |
| Gleason score, No. (%) | |
| ≤7 | 109 (32.0) |
| ≥8 | 189 (55.5) |
| Unknown | 43 (12.6) |
| Histology, No. (%) | |
| Acinar adenocarcinoma | 308 (90.3) |
| Presentation of disease at diagnosis, No. (%) | |
| De novo | 211 (61.9) |
| Recurrent | 130 (38.1) |
| Sites of metastasis at Cyc initiation, No. (%) | |
| Bone | 318 (93.3) |
| Lymph nodes | 161 (47.2) |
| Visceral | 45 (13.2) |
| Previous treatment lines, No. (%) | |
| ≤Two lines | 132 (38.7) |
| >Two lines | 209 (61.3) |
| Previous lines, No. (%) | |
| Docetaxel | 251 (73.6) |
| First-generation ARSI | 292 (85.6) |
| Novel-generation ARSI | 34 (10.0) |
| Platinum-based chemotherapy | 11 (3.2) |
Abbreviations: ARSI, androgen receptor signaling inhibitor; Cyc, oral cyclophosphamide; ECOG-PS, Eastern Cooperative Oncology Group performance status.
Outcomes
After treatment with oral cyclophosphamide, any PSA decrease occurred in 33.4% of patients (n = 114), with 19.6% (n = 67) having a PSA decrease of 30% or more from baseline, 13.2% (n = 45) having a PSA decrease of 50% or more from baseline (PSA50 response), and 2.6% (n = 9) having a PSA decrease of 90% or more from baseline (Fig 2). Of the 236 patients who reported bone pain at baseline, almost half reported pain improvement after treatment with cyclophosphamide (n = 114, 48.3%).
FIG 2.
Waterfall plot showing PSA variation from baseline after treatment with oral cyclophosphamide. PSA, prostate-specific antigen; PSA30, prostate-specific antigen decrease ≥30% from baseline; PSA50, prostate-specific antigen decrease ≥50% from baseline.
Median treatment duration was 2.1 months (IQR, 1.4-3.8; range, 0.3-51.9). Ten patients were treated for 12 or more months, and two patients were treated for 24 or more months, maintaining PSA response and clinical benefit (Fig 3). Two additional patients had pauses during cycles and were treated with cyclophosphamide for more than 24 months if considered since the first exposition. Patients who achieved a PSA50 response had a longer time on treatment compared with those who had no PSA50 response (7.0 v 1.7 months; P < .01; Fig 4). PSA50 responses were more frequent among patients who had not previously received docetaxel (21.1% v 10.4%; P = .01) and among those who had ECOG 0 or 1 (17.9% v 8.0%; P = .007), but there were no differences in PSA50 response according to the presence of visceral metastasis (P = .98), de novo disease presentation (P = .78), or the use of two or more previous lines of therapy (P = .07; Appendix Table A1).
FIG 3.
Swimmer plot of patients with a PSA50 response after oral cyclophosphamide. Median treatment duration was 2.1 months, with 10 patients being treated for more than 12 months. PSA50, prostate-specific antigen decrease ≥50% from baseline.
FIG 4.
Overall survival of the full cohort (A) of patients treated with oral cyclophosphamide and (B) PSA50 responders (yellow) versus PSA50 nonresponders (blue). Time on treatment of the full cohort (C) of patients treated with oral cyclophosphamide and (D) PSA50 responders (yellow) versus PSA50 nonresponders (blue). mDoT, median duration on treatment; mOS, median overall survival; PSA50, prostate-specific antigen decrease ≥50% from baseline.
After a median follow-up of 58.1 months, the median OS was 9.9 months (95% CI, 8.5 to 11.2; Fig 4). Patients who achieved a PSA50 response had longer OS than those with no PSA50 response (21.8 v 9.2 months; P < .01). Patients with visceral metastasis, ECOG status ≥2, previous docetaxel use, and neutrophil-to-lymphocyte ratio higher than three had poorer survival in the univariate analysis (Table 2). After performing a multivariate analysis considering the factors mentioned above, all remained statistically associated with poorer survival (Table 3).
TABLE 2.
Univariate Analysis of Baseline Factors and OS
| Variable | OS, Median (95% CI) | Univariate Analysis | |
|---|---|---|---|
| HR (95% CI) | P | ||
| ECOG-PS | |||
| 0-1 | 14.8 (13.1 to 16.9) | 2.9 (2.3 to 3.8) | 2.2 × 10–6 |
| ≥2 | 6.1 (5.3 to 7.2) | ||
| Previous docetaxel | |||
| No | 12.4 (10.3 to 17.4) | 1.7 (1.3 to 2.3) | 6.9 × 10–5 |
| Yes | 9.2 (7.7 to 10.4) | ||
| Visceral metastasis | |||
| No | 10.4 (9.5 to 12.0) | 1.8 (1.3 to 2.7) | .004 |
| Yes | 7.3 (5.3 to 8.6) | ||
| Previous therapies | |||
| >2 | 10.0 (8.6 to 12.3) | 1.1 (0.8 to 1.4) | .6 |
| ≤2 | 9.5 (7.8 to 11.7) | ||
| De novo metastatic disease | |||
| No | 10.4 (8.4 to 11.6) | 0.9 (0.7 to 1.1) | .2 |
| Yes | 9.5 (8.3 to 11.6) | ||
| Neutrophil-to-lymphocyte ratio | |||
| ≤3 | 11.1 (9.8 to 14.2) | 1.4 (1.1 to 1.7) | .008 |
| >3 | 8.5 (7.2 to 10.6) | ||
| Continuous | — | 1.04 (1.0 to 1.1) | .0008 |
| Eosinophil-to-lymphocyte ratio | |||
| ≤0.1 | 9.5 (8.3 to 11.2) | 1.03 (0.8 to 1.3) | .8 |
| >0.1 | 10.6 (8.5 to 13.4) | ||
| Continuous | — | 1.1 (0.6 to 2.0) | .3 |
Abbreviations: ECOG-PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; OS, overall survival.
TABLE 3.
Multivariate Analysis of Baseline Factors and OS
| Variable | OS, Median (95% CI) | Multivariate Analysis | |
|---|---|---|---|
| HR (95% CI) | P | ||
| ECOG-PS | |||
| 0-1 | 14.8 (13.1 to 16.9) | 2.8 (2.2 to 3.6) | 2 × 10–6 |
| ≥2 | 6.1 (5.3 to 7.2) | ||
| Previous docetaxel | |||
| No | 12.4 (10.3 to 17.4) | 1.7 (1.3 to 2.3) | .0001 |
| Yes | 9.2 (7.7 to 10.4) | ||
| Visceral metastasis | |||
| No | 10.4 (9.5 to 12.0) | 1.7 (1.2 to 2.5) | .002 |
| Yes | 7.3 (5.3 to 8.6) | ||
| Neutrophil-to-lymphocyte ratio | |||
| ≤3 | 11.1 (9.8 to 14.2) | 1.2 (0.99 to 1.6) | .057 |
| >3 | 8.5 (7.2 to 10.9) | ||
| Continuous | — | 1.02 (1.00 to 1.04) | .03 |
Abbreviations: ECOG-PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; OS, overall survival.
Data from the per-protocol population were consistent with the results presented. Median OS was 10.4 months (95% CI, 9.4 to 12) and those who achieved PSA50 response had longer survival (9.7 v 21.8 months). Median treatment duration was 2.5 months (IQR, 1.6-4.0) and those with PSA50 response remained longer on treatment than those without response (7.0 v 1.8 months; Appendix Fig A1).
Safety and Toxicities
Twenty-six patients (7.6%) were hospitalized because of toxicities, and 26 (7.6%) required blood transfusion while on treatment with oral metronomic cyclophosphamide. Fifty-six patients (16.4%) discontinued treatment and 25 (7.4%) required dose reductions because of toxicities. Most of the patients who suspended treatment had ECOG 2 or greater (57.1%) before cyclophosphamide initiation and were subsequently treated with best supportive care (n = 35, 62.5%), followed by another line of hormonal therapy (n = 12, 21.4%) or chemotherapy (n = 8, 14.3%). Among patients who suspended treatment, PSA50 response was 8.9% and median OS was 7.8 months (95% CI, 5.8 to 10.4).
DISCUSSION
Cyclophosphamide is an alkylating agent that has been used in prostate cancer since the 1990s.13 It has cytotoxic and immunosuppressive properties at high doses, and at low doses, it exerts antiangiogenic and immunostimulant properties through inhibition of regulatory T cells.12,14 Oral metronomic cyclophosphamide was studied in multiple studies, mostly retrospective combined with corticosteroids, with a PSA50 response rate ranging from 24% to 44% (Table 4).12,13,15-26
TABLE 4.
Studies Reporting the Use of Cyclophosphamide for Patients With Metastatic Castration-Resistant Prostate Cancer
| First Author | Year | Study Type | Sample Size | Previous Chemotherapy | PSA50 response, n (%) | Objective Response Rate, Number of Patients (%) | Reference |
|---|---|---|---|---|---|---|---|
| Raghavan et al | 1993 | Retrospective | 30 | NR | NR | 6 (20) | 12 |
| Wozniak et al | 1993 | Retrospective | 52 | NR | NR | 2/29 (7) | 15 |
| Glode et al | 2003 | Retrospective | 34 | 13 | 13 (41) | NR | 16 |
| Hellerstedt et al | 2003 | Phase II | 37 | 15 | 15 (42) | 1/16 (6) | 17 |
| Lord et al | 2007 | Phase II | 58 | NR | 34 | NR | 18 |
| Fontana et al | 2009 | Prospective | 28 | 19 | 9/28 (32) | 1/5 (25) | 19 |
| Ladoire et al | 2010 | Prospective | 23 | 23 | 6/23 (26) | NR | 20 |
| Gebbia et al | 2011 | Phase II | 58 | 58 | 15/58 (25) | 3/17 (18) | 21 |
| Jeong et al | 2016 | Retrospective | 49 | 29 | 19/49 (39) | 13/49 (65) | 22 |
| Dabkara et al | 2018 | Retrospective | 18 | 13 | 5/18 (27) | NR | 23 |
| Calvani et al | 2019 | Retrospective | 37 | 29 | 17/37 (51) | 3/12 (25) | 24 |
| Knipper et al | 2019 | Retrospective | 14 | 14 | 2/13 (15) | NR | 25 |
| Mar et al | 2023 | Retrospective | 43 | 41 | 9/43 (20.9) | NR | 26 |
| Pineda et al | 2024 | Retrospective | 341 | 251 | 45/341 (13.2) | NR | Present paper |
Abbreviations: NR, not reported; PSA50, prostate-specific antigen decrease ≥50% from baseline.
Owing to its reduced toxicity, low cost, and ease of use, oral metronomic cyclophosphamide was used in the past as a line of treatment of patients with mCRPC. However, given the emergence of more modern life-prolonging therapies, cyclophosphamide is currently seen as anachronic and is now rarely used in private clinical practice. However, in the public setting of developing countries, where health care resources are limited and access to novel agents is still not feasible, oral cyclophosphamide can be considered as a potentially active line of treatment.
To our knowledge, this is the largest real-world cohort of patients with mCRPC treated with oral cyclophosphamide published to date. Among these heavily pretreated patients, cyclophosphamide showed a PSA50 response rate of 13%. PSA50 responses correlated with increased OS and time on treatment in this cohort. Of note, several patients had long-term responses, clearly benefiting from treatment.
Predictors of response were analyzed and included no prior chemotherapy use and ECOG-PS 0 or 1. Neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios were not correlated with outcomes. Cyclophosphamide was well tolerated with only 16.4% discontinuing treatment because of toxicity and 7.6% hospitalized because of toxicities. Blood transfusion required for 26 patients while on treatment.
Our study has several limitations, and the results should be interpreted with caution. First, its retrospective nature precludes a deeper understanding of potential biomarkers predictive of response and limits a more granular evaluation of toxicities associated with oral cyclophosphamide. Second, there is a possibility of selection bias and overestimation of responses. It should also be noted that most of the patients were not treated with modern life-prolonging treatments such as novel antiandrogens and targeted therapies, as these are not reimbursed options in Brazil's public health system.
In conclusion, cyclophosphamide is active against a small proportion of patients with mCRPC, with a favorable toxicity profile. It can be considered as a line of treatment specifically in scenarios of limited health care resources.
ACKNOWLEDGMENT
The authors are grateful to the patients and their families.
APPENDIX
FIG A1.
Overall survival of the per-protocol population (A) treated with oral cyclophosphamide and (B) PSA50 responders (yellow) versus PSA50 nonresponders (blue). Time on treatment of the per-protocol population (C) treated with oral cyclophosphamide and (D) PSA50 responders (yellow) versus PSA50 nonresponders (blue). mDoT, median duration on treatment; mOS, median overall survival; PSA50, prostate-specific antigen decrease ≥50% from baseline.
TABLE A1.
PSA50 Response in Different Subgroups
| Variable | Proportion of Patients Achieving PSA ≥50% Response, % | OR (95% CI) | P |
|---|---|---|---|
| ECOG | |||
| 0-1 | 17.9 | 1 | .007 |
| ≥2 | 8.0 | 0.4 (0.2 to 0.8) | |
| Previous docetaxel | |||
| No | 21.1 | 1 | .009 |
| Yes | 10.4 | 0.4 (0.2 to 0.8) | |
| Presence of visceral metastasis | |||
| No | 13.2 | 1 | .98 |
| Yes | 13.3 | 1.01 (0.4 to 2.5) | |
| Number of previous therapies | |||
| ≥2 | 10.5 | 1 | .07 |
| <2 | 17.4 | 1.8 (0.9 to 3.3) | |
| De novo metastatic disease | |||
| No | 13.8 | 1 | .78 |
| Yes | 12.8 | 0.9 (0.5 to 1.7) |
Abbreviations: ECOG, Eastern Cooperative Oncology Group; OR, odds ratio; PSA, prostate-specific antigen; PSA50, prostate-specific antigen decrease ≥50% from baseline.
PRIOR PRESENTATION
Presented at the ASCO Genitourinary Cancers Symposium 2024, San Francisco, CA, January 29, 2024 (abstr 150).
AUTHOR CONTRIBUTIONS
Conception and design: Diana del Cisne Pineda, Gabriel Berlingieri Polho, Vivian Naomi Horita, Jamile Almeida Silva, Guilherme Fialho de Freitas, Paulo M. Hoff, José Mauricio Mota
Financial support: José Mauricio Mota
Administrative support: Paulo M. Hoff, José Mauricio Mota
Provision of study materials or patients: Joao Carlos Resende, Jamile Almeida Silva, Paulo M. Hoff, José Mauricio Mota
Collection and assembly of data: Diana del Cisne Pineda, Yumi Ricucci Shinkado, Nathalia de Souza Crusoe, Vivian Naomi Horita, David Queiroz Muniz, José Mauricio Mota
Data analysis and interpretation: Diana del Cisne Pineda, Gabriel Berlingieri Polho, Yumi Ricucci Shinkado, Gustavo Alves Contado, Nathalia de Souza Crusoe, Vivian Naomi Horita, Joao Carlos Resende, Jamile Almeida Silva, David Queiroz Muniz, Caio V. Suartz, Leopoldo Alves Ribeiro-Filho, Paulo M. Hoff, José Mauricio Mota
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Gabriel Berlingieri Polho
Travel, Accommodations, Expenses: Libbs
Guilherme Fialho de Freitas
Honoraria: MSD
Consulting or Advisory Role: BMS Brazil
Speakers' Bureau: MSD
David Queiroz Muniz
Consulting or Advisory Role: Janssen Oncology
Speakers' Bureau: Janssen, BMS Brazil, Bayer, Ferring, Pfizer
Research Funding: Pfizer (Inst)
Leopoldo Alves Ribeiro-Filho
Research Funding: MSD (Inst)
Paulo M. Hoff
Leadership: Oncologia D'Or
Stock and Other Ownership Interests: Oncostar
Honoraria: Bayer Health (I), United Medical (I)
Consulting or Advisory Role: United Health Group (I), Bayer (I), Lilly (I), Exelixis (I), EMS, AstraZeneca (Inst)
Research Funding: Bayer (Inst), MSD Oncology (Inst), Novartis (Inst), Exelixis (Inst), Roche/Genentech (Inst), AstraZeneca/MedImmune (Inst), Lilly (I), BMS Brazil (Inst)
Uncompensated Relationships: AstraZeneca
José Mauricio Mota
Honoraria: Janssen, Zodiac Pharma, Astellas Pharma, Bayer, Ipsen, Pfizer, AstraZeneca, Amgen, Merck, Novartis
Consulting or Advisory Role: Janssen Oncology, Astellas Pharma
Speakers' Bureau: Janssen Oncology, Amgen, Zodiac Pharma, Bayer, Astellas Pharma, Ipsen, Pfizer, AstraZeneca, Merck, Novartis
Research Funding: Bayer
Expert Testimony: Bayer, Astellas Pharma, Adium Pharma
Travel, Accommodations, Expenses: Zodiac Pharma, Janssen Oncology
No other potential conflicts of interest were reported.
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