Responses of Renal Cell Carcinomas to 29 Different Systemic Anti-Cancer Therapies
Main Article Content
Abstract
Introduction: The prevailing view is that renal cell carcinomas (RCCs) are resistant to chemotherapy. However, it is essential to periodically reassess paradigms. When RCC is diagnosed concurrently with another malignancy, the latter typically assumes priority in treatment. This scenario provides a unique opportunity to observe the effects of systemic therapy on the RCC, without incurring additional costs or risks to the patient. Our study aimed to explore the response of several "old school" and modern anti-cancer systemic therapies on growth rate of otherwise untreated RCC.
Methods: Twenty patients (average age 61.4 years, SD 10.0 years) were diagnosed with histologically confirmed RCC and another type of cancer. These included lymphomas (7 patients), lung adenocarcinoma, and breast cancer (4 patients each), leukemia (3 patients), and 4 patients with other types of malignancy. The cohort received 29 different systemic chemotherapeutic agents, including cyclophosphamide and doxorubicin (5 patients each), and prednisone, vincristine, and rituximab (4 patients each). The patients were monitored radiographically, focusing on RCC, without any RCC-specific treatments. Changes in RCC diameter on axial CT scans were recorded during the follow-up period.
Results: The average RCC diameter on initial CT scans was 41.9 ± 25.1 mm. After an average follow-up of 28.9 ± 29.6 months, the RCC diameter increased in 14 patients (by an average rate of 7.3 ± 2.9 mm/year), while it remained stable or decreased in six patients. Notably, tumor size reductions were observed in patients treated with Tamoxifen and a combination of bevacizumab, docetaxel, and cisplatin.
Conclusions: These results underscore the significant resistance of RCC to both traditional chemotherapies and newer treatments, many of which have not been specifically evaluated in the context of RCC. However, several agents demonstrated potential efficacy and merit further investigation. Nevertheless, no solid conclusion can be drawn regarding any specific agent using this methodology.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Diamond E, Molina AM, Carbonaro M, Akhtar NH, et al. Cytotoxic chemotherapy in the treatment of advanced renal cell carcinoma in the era of targeted therapy. Crit Rev Oncol Hematol. 2015; 96:518-26. doi: 10.1016/j.critrevonc.2015.08.007. Epub 2015 Aug 13. PMID: 26321263.
3. Tsimafeyeu I, Demidov L, Kharkevich G, et al. Phase II, multicenter, uncontrolled trial of single-agent capecitabine in patients with non-clear cell metastatic renal cell carcinoma. Am J Clin Oncol. 2012;35:251-4. doi: 10.1097/COC.0b013e31820d bc17. PMID: 21358295.
4. Mani S, Vogelzang NJ, Bertucci D, et al. Phase I study to evaluate multiple regimens of intravenous 5-fluorouracil administered in combination with weekly gemcitabine in patients with advanced solid tumors: a potential broadly active regimen for advanced solid tumor malignancies. Cancer. 2001; 92:1567-76. doi: 10.1002/1097-0142(20010915)92 :6<1567::aid-cncr1483>3.0.co;2-l. PMID: 11745236.
5. Ryan CW, Vogelzang NJ, Stadler WM. A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with metastatic renal cell carcinoma. Cancer. 2002;94:2602-9. doi: 10.1002/cncr.10528. PMID: 12173327.
6. Posadas EM, Limvorasak S, Figlin RA. Targeted therapies for renal cell carcinoma. Nat Rev Nephrol. 2017;13:496-511. doi: 10.1038/nrneph.2017.82. Epub 2017 Jul 10. PMID: 28691713.
7. Tung I, Sahu A. Immune Checkpoint Inhibitor in First-Line Treatment of Metastatic Renal Cell Carcinoma: A Review of Current Evidence and Future Directions. Front Oncol. 2021;11:707214. doi: 10.3389/fonc.2021.707214. PMID: 34527581; PMCID: PMC8435744.
8. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378:1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21. PMID: 29562145; PMCID: PMC5972549.
9. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380:1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16. PMID: 30779529.
10. Motzer RJ, Escudier B, George Set al. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. 2020; 126:4156-4167. doi: 10.1002/cncr.33033. Epub 2020 Jul 16. PMID: 32673417; PMCID: PMC8415096.
11. Richard PO, Jewett MA, Bhatt JR, et al. Renal Tumor Biopsy for Small Renal Masses: A Single-center 13-year Experience. Eur Urol. 2015;68:1007-13. doi: 10.1016/j.eururo.2015.04.004. Epub 2015 Apr 18. PMID: 25900781.
12. Chawla SN, Crispen PL, Hanlon AL et al. The natural history of observed enhancing renal masses: meta-analysis and review of the world literature. J Urol. 2006;175: 425-31. doi: 10.1016/S0022-5347 (05)00148-5. PMID: 16406965.
13. Jewett MA, Mattar K, Basiuk J, et al. Active surveillance of small renal masses: progression patterns of early stage kidney cancer. Eur Urol. 2011;60:39-44. doi: 10.1016/j.eururo.2011.03.030. Epub 2011 Apr 1. PMID: 21477920.
14. Mues AC, Haramis G, Badani K et al. Active surveillance for larger (cT1bN0M0 and cT2N0M0) renal cortical neoplasms. Urology;2010;76:620-623. doi: 10.1016/j.urology.2010.04.021. PMID: 20599256.
15. Mehrazin R, Smaldone MC, Kutikov A et al. Growth kinetics and short-term outcomes of cT1b and cT2 renal masses under active surveillance. J Urol;192:659-664. doi: 10.1016/j.juro.2014.03.038. Epub 2014 Mar 15. PMID: 24641909; PMCID: PMC4419692.
16. Staehler M, Haseke N, Stadler T et al. The growth rate of large renal masses opposes active surveillance. BJU Int;105:928-931. doi: 10.1111/j.1464-410X.2009.08840.x. Epub 2009 Sep 14. PMID: 197 51265.
17. Greene FL, Page DL, Flemming ID et al. American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer:2002:323-5. https://link.springer.com/book/10.1007/978-1-4757-3656-4
18. Störkel S, Eble JN, Adlakha DK, et al. Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer;1997;80:987-9. doi: 10.1002/(sici)1097-0142(19970901)80:5<987::aid-cncr24>3.0.co;2-r. PMID: 9307203.
19. Fuhrman SA, Lasky LC. Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol;1982;655-653. doi: 10.1097/00000478-198210000-00007. PMID: 71 80965.
20. Mues AC, Landman J. Small renal masses: current concepts regarding the natural history and reflections on the American Urological Association guidelines. Curr Opin Urol. 2010;20:105-10.
doi: 10.1097/MOU.0b013e32833625f8. PMID: 200 75734.
21. Li XS, Yao L, Gong K et al. Growth pattern of renal cell carcinoma (RCC) in patients with delayed surgical intervention. J Cancer Res Clin Oncol. 2013;138:269-274. doi: 10.1007/s00432-011-1083-0. Epub 2011 Nov 22. PMID: 22105897.
22. Walsh N, Larkin A, Kennedy S, et al. Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma. BMC Urol. 2009;9:6. doi: 10.1186/1471-2490-9-6. PMID: 19552816; PMCID: PMC2723136.
23. McFadyen MC, Melvin WT, Murray GI. Cytochrome P450 CYP1B1 activity in renal cell carcinoma. Br J Cancer. 200491:966-71. doi: 10.103 8/sj.bjc.6602053. PMID: 15280921; PMCID: PMC240 9861.
24. Selvarajah J, Nathawat K, Moumen A, et al. Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways. Cell Death Dis. 2013: 17;4(10):e865. doi: 10.1038/cddis.2013.395. PMID: 24136229; PMCID: PMC3920935.
25. Aweys H, Lewis D, Sheriff M, et al. Renal Cell Cancer - Insights in Drug Resistance Mechanisms. Anticancer Res. 2023;43:4781-4792. doi: 10.2187 3/anticanres.16675. PMID: 37909991.
26. Mickisch GH, Roehrich K, Koessig J, et al. Mechanisms and modulation of multidrug resistance in primary human renal cell carcinoma. J Urol. 1990; 144:755-9. doi: 10.1016/s0022-5347(17)39586-1. PMID: 1974934.
27. Amin R. Tamoxifen-induced regression of pulmonary metastases from renal cell carcinoma. Br J Radiol. 1983;56:766-7. doi: 10.1259/0007-1285-56-670-766. PMID: 6616143.
28. Atzpodien J, Kirchner H, Illiger HJ, et al. IL-2 in combination with IFN- alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer. 2001;85:1130-6. doi: 10.1054/bjoc.20 01.2076. PMID: 11710825; PMCID: PMC2375150.
29. Al-Sarraf M, Eyre H, Bonnet J, et al. Study of tamoxifen in metastatic renal cell carcinoma and the influence of certain prognostic factors: a Southwest Oncology Group Study. Cancer Treat Rep. 1981; 65:447-51. PMID: 7237466.
30. Bielcikova Z, Werner L, Stursa J, et al. Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial. Ther Adv Med Oncol. 2023;30;15:17588359231197957. doi: 10.1177/17588359231197957. PMID: 377865 38; PMCID: PMC10541747.
31. Rixe O, Bukowski RM, Michaelson MD, et al. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007;8:975-84. doi: 10.1016/S1470-2045(07)70285-1. Epub 2007 Oct 23. PMID: 1795 9415.
32. Johnson L, Bylund J, Strup S, et al. Concomitant Renal Cell Carcinoma and Hematologic Malignancy in Immunosuppressed Patients. Am J Med Sci. 2016; 351:480-4. doi: 10.1016/j.amjms.2016.02.027. Epub 2016 Mar 21. PMID: 27140706.