Aktueller Stand der Chemotherapie in der Behandlung des fortgeschrittenen Peniskarzinoms

Zusammenfassung

Die Prognose des fortgeschrittenen Peniskar­zinoms ist äußerst schlecht. Aufgrund der ­Seltenheit dieser Erkrankung, der schwachen Studienlage zur Chemotherapie sowie der dezentralisierten Behandlung hat sich die Prognose in den letzten Jahrzehnten auch nicht verbessert. Basierend auf aktuellen Studiendaten sollte bei einem lokal fortgeschrittenen Peniskarzinom mit regionalen Lymphknotenmetastasen ein multimodales Therapiekonzept bestehend aus Lymphadenektomie und perioperativen ­cisplatin-/taxanhaltigen Chemotherapieregime angestrebt werden. Mit der systematischen, zentralisierten Erfassung und Analyse der Behandlungsdaten durch das Rostocker-AUO-Peniskarzinomregister soll die Situation für Patienten mit Peniskarzinom weiter verbessert werden. Eine mögliche, bislang überwiegend in Einzelfällen untersuchte Therapieoption stellen Targettherapeutika dar. Ob sie sich in der Therapielandschaft etablieren können, müssen weitere prospektive Untersuchungen klären. Die Indikation zur palliativen Chemotherapie des fortgeschrittenen Peniskarzinoms sollte insbesondere unter Berücksichtigung des Allgemeinzustandes und Alters des Patienten sowie in Hinblick auf eventuell auftretende chemotherapieassoziierte Toxizitäten stets kritisch gestellt werden. Eine Abwägung zum „Best supportive care“-Konzept ist hier unerlässlich. Der Artikel soll einen Überblick über wesentliche Entwicklungen und klinische Studien zur Chemotherapie des Peniskarzinoms geben.

Abstract

The prognosis of advanced penile carcinomas is extremely poor. Low numbers of available studies on chemotherapy over a long time, decentralized treatment as well as rareness of disease have not improved the prognosis. This article focuses on important clinical trials and developments for chemotherapy in penile cancer. Considering the latest study data there is a strong recommendation for multimodal approaches, including lymph node dissection and perioperative treatments with cisplatin/taxane-based chemotherapy. A systematic, centralized registration and evaluation by the “Rostocker-AUO-Register” for penile cancer should improve conditions for affected patients. Furthermore, molecular targeted therapy might be a promising therapeutic option but until now only very few case reports have been published. Further prospective clinical trials are necessary to establish these agents in the therapeutic landscape of penile cancer. Decision for palliative chemotherapy in advanced penile cancer should be well considered and depends on the patient’s age and general condition particularly regarding possible adverse events of chemotherapy. Notably, best supportive care might be an important alternative for some patients and should be taken in consideration.

Schlüsselwörter

Peniskarzinom - Lymphknotenmetastasen - Chemotherapie - Targettherapie - AUO

Key words

penile cancer - lymph node metastases - chemotherapy - targeted therapy - AUO

• Literatur

• 1 Protzel C, Ruppin S, Milerski S et al. The current state of the art of chemotherapy of penile cancer: Results of a nationwide survey of German clinics. Urologe A 2009;
• 2 Pizzocaro G, Algaba F, Horenblas S et al. EAU Penile Cancer Guidelines 2009. Eur Urol
• 3 Protzel C, Alcaraz A, Horenblas S et al. Lymphadenectomy in the surgical management of penile cancer. Eur Urol 2009; 55: 1075-1088
• 4 Culkin DJ, Beer TM. Advanced penile carcinoma. J Urol 2003; 170: 359-365
• 5 Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol 1988; 27: 823-824
• 6 Leijte JA, Kerst JM, Bais E et al. Neoadjuvant chemotherapy in advanced penile carcinoma. Eur Urol 2007; 52: 488-494
• 7 Theodore C, Skoneczna I, Bodrogi I et al. A phase II multicentre study of irinotecan (CPT 11) in combination with cisplatin (CDDP) in metastatic or locally advanced penile carcinoma (EORTC PROTOCOL 30992). Ann Oncol 2008;
• 8 Pizzocaro G, Nicolai N, Milani A. Taxanes in Combination with Cisplatin and Fluorouracil for Advanced Penile Cancer: Preliminary Results. Eur Urol 2008;
• 9 Pagliaro LC, Williams DL, Daliani D et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol 28: 3851-3857
• 10 Protzel C, Hakenberg OW. Penile carcinoma: diagnosis and therapy. Urologe A 2013; 52: 87-98
• 11 Pizzocaro G, Piva L, Bandieramonte G et al. Up-to-date management of carcinoma of the penis. Eur Urol 1997; 32: 5-15
• 12 Franks KN, Kancherla K, Sethugavalar B et al. Radiotherapy for node positive penile cancer: experience of the Leeds teaching hospitals. J Urol 186: 524-529
• 13 Hakenberg OW, Nippgen JB, Froehner M et al. Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma. BJU Int 2006; 98: 1225-1227
• 14 Noronha V, Patil V, Prabhash K. Role of paclitaxel and platinum based adjuvant chemotherapy in high risk penile cancer. Urology Annals 2012; 4: 150-153
• 15 Preis E, Jakse G. Options in palliative therapy for penile cancer. Urologe A 2007; 46: 49-53
• 16 Heinlen JE, Buethe DD, Culkin DJ. Advanced penile cancer. Int Urol Nephrol 2012; 44: 139-148
• 17 Paul R, van Randenborgh H, Scholer S et al. Penile cancer – aftercare with results. How much is necessary?. Urologe A 2005; 44: 1031-1036
• 18 Dexeus FH, Logothetis CJ, Sella A et al. Combination chemotherapy with methotrexate, bleomycin and cisplatin for advanced squamous cell carcinoma of the male genital tract. J Urol 1991; 146: 1284-1287
• 19 Corral DA, Sella A, Pettaway CA et al. Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: a phase II study of methotrexate, cisplatin and bleomycin. J Urol 1998; 160: 1770-1774
• 20 Haas GP, Blumenstein BA, Gagliano RG et al. Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol 1999; 161: 1823-1825
• 21 Kattan J, Culine S, Droz JP et al. Penile cancer chemotherapy: twelve years’ experience at Institut Gustave-Roussy. Urology 1993; 42: 559-562
• 22 Protzel C, Hakenberg OW. Chemotherapy in patients with penile carcinoma. Urol Int 2009; 82: 1-7
• 23 Hussein AM, Benedetto P, Sridhar KS. Chemotherapy with cisplatin and 5-fluorouracil for penile and urethral squamous cell carcinomas. Cancer 1990; 65: 433-438
• 24 Di Lorenzo G, Buonerba C, Federico P et al. Cisplatin and 5-fluorouracil in inoperable, stage IV squamous cell carcinoma of the penis. BJU Int 2012; 110: E661-E666
• 25 Shammas FV, Ous S, Fossa SD. Cisplatin and 5-fluorouracil in advanced cancer of the penis. J Urol 1992; 147: 630-632
• 26 Salvioni R, Nicolai N, Piva L et al. Pilot study of cisplatin, 5-fluorouracil, and a taxan (TPF) for advanced squamos cell carcinoma (SCC) of the penis. J Clin Oncol 2011; 29 (abstr 4639)
• 27 Nicholson S, Hall E, Harland SJ et al. Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer 2013; 109: 2554-2559
• 28 Liu JY, Li YH, Liu ZW et al. Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent squamous cell carcinoma of the penis. Chin J Cancer 2013;
• 29 Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 2004; 59: 21-26
• 30 Gold KA, Lee HY, Kim ES. Targeted therapies in squamous cell carcinoma of the head and neck. Cancer 2009; 115: 922-935
• 31 Gou HF, Li X, Qiu M et al. Epidermal growth factor receptor (EGFR)-RAS signaling pathway in penile squamous cell carcinoma. PLoS One 2013; 8: e62175
• 32 Di Lorenzo G, Perdona S, Buonerba C et al. Cytosolic phosphorylated EGFR is predictive of recurrence in early stage penile cancer patients: a retropective study. J Transl Med 2013; 11: 161
• 33 Carthon BC, Pettaway C, Pagliaro LC. Epidermal growth factor receptor (EGFR) targeted therapy in advanced metastatic squamous cell carcinoma (AMSCC) of the penis: updates and molecular analyses. J Clin Oncol 2010; 28 (Suppl)
• 34 Carthon BC, Ng CS, Pettaway CA et al. Epidermal Growth Factor Receptor-Targeted Therapy in Locally Advanced or Metastatic Squamous Cell Carcinoma of the Penis. BJU Int 2013;
• 35 Necchi A, Nicolai N, Colecchia M et al. Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis. J Clin Oncol 2011; 29: e650-e652
• 36 Brown A, Ma Y, Danenberg K et al. Epidermal growth factor receptor-targeted therapy in squamous cell carcinoma of the penis: a report of 3 cases. Urology 2014; 83: 159-165
• 37 Zhu Y, Li H, Yao XD et al. Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report. Urol Int 2010; 85: 334-340