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German Testicular Cancer Study Group Cooperative Study
TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY
argued that not all port sites need fascial closure. Several cases of port-site hernia, however, have been reported recently with the use of bladeless trocars. This study evaluated the incidence of port-site hernias after robot-assisted radical prostatectomy (RARP) as we routinely closed the fascia of only the midline 12-mm port site. Patients and Methods: From 2006 to 2009, 498 patients with localized prostate cancer underwent RARP. Bladeless dilating trocars were used in all of our patients. Routinely, six ports were used: two 12 mm, three 8 mm, and one 5 mm. Fascial closure was performed only for the midline supraumbilical 12-mm port site. Results: In 498 cases of RARP, there were two port-site hernias (0.4%, 2/498). Both cases occurred at the midline supraumbilical 12-mm camera port site. No hernia developed at nonmidline port sites, including the lateral 12-mm port site. Conclusion: Trocar site hernias after RARP are rare. When bladeless dilating trocars are used, routine closure of fascia of non-midline 12-mm or smaller port sites is not necessary. Splitting the muscle and fascia without cutting likely renders routine closure of fascia unnecessary for nonmidline ports that are ⱕ12 mm. Editorial Comment: With more surgeons performing robot-assisted laparoscopy who have not undergone classic laparoscopy training, it is worth revisiting basic principles of laparoscopy. Although I have heard of anecdotal cases of nonmidline port site hernias, the incidence is incredibly low. In this series of approximately 1,500 nonmidline port sites, of which 1,000 were either 8 or 12 mm ports, not a single hernia was reported using dilating trocars. I also do not routinely close these fascial defects, but if there is any doubt, the surgeon should at least inspect each, and if the index finger can pass through the fascia, then the fascia should be closed. Jeffrey A. Cadeddu, M.D.
Urological Oncology: Testis Cancer and Advances in Oncological Therapy Preclinical and Clinical Activity of Sunitinib in Patients with Cisplatin-Refractory or Multiply Relapsed Germ Cell Tumors: A Canadian Urologic Oncology Group/ German Testicular Cancer Study Group Cooperative Study K. Oechsle, F. Honecker, T. Cheng, F. Mayer, P. Czaykowski, E. Winquist, L. Wood, M. Fenner, S. Glaesener, J. T. Hartmann, K. Chi, C. Bokemeyer and C. Kollmannsberger Division of Oncology, Hematology and Bone Marrow Transplantation, Section of Pneumology, University Medical Centre Eppendorf, Hamburg University, Hamburg, Germany Ann Oncol 2011; 22: 2654 –2660.
Background: The objective of the study was to investigate the activity of sunitinib in a cell line model and subsequently in patients with cisplatin-refractory or multiply relapsed germ cell tumors (GCT). Methods: The effect of sunitinib on cell proliferation in cisplatin-sensitive and cisplatin-refractory GCT cell lines was evaluated after 48-h sunitinib exposure by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide] assay, and IC(50) (concentration that causes 50% inhibition of growth) doses were determined. Sunitinib was subsequently administered at a dose of 50 mg/day for 4 weeks followed by a 2-week break to 33 patients using a Simon two-stage design. Results: Sunitinib demonstrated comparable dose-dependent growth inhibition in cisplatin-sensitive and cisplatinresistant cell lines, with IC(50) between 3.0 and 3.8 M. Patient characteristics were as follows: median of 2 (1– 6) cisplatin-containing regimens; high-dose chemotherapy 67%; late relapse 33%; and cisplatin refractory or absolute cisplatin refractory 54%. Toxic effects included fatigue (39%), anorexia (21%), diarrhea (27%), mucositis (45%), nausea (33%), hand-foot syndrome (12%), dyspepsia (27%), and skin rash (18%). No unexpected side-effects were observed. Thirty-two of 33 patients were
533
534
TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY
assessable for response. Three confirmed partial responses (PRs) and one unconfirmed PR were seen for a total response rate of 13%. Median progression-free survival (PFS) was 2 months, with a 6-month PFS rate of 11%. Conclusions: Sunitinib shows in vitro activity in cisplatin-resistant GCT cell lines. Modest clinical activity in heavily pretreated GCT patients was observed. Editorial Comment: The majority of cases of germ cell tumor are cured with cisplatin based regimens. However, patients who relapse after cisplatin based therapy or high dose chemotherapy have generally a poor prognosis. Various agents have been examined, including single agents such as paclitaxel, gemcitabine, etoposide and oxaliplatin. Different combinations have shown response rates up to 50%, including a 10% long-term survival rate, although generally duration of remission is moderate. Mismatch repair deficiency and microsatellite instability are thought to be associated with cisplatin resistance in human germ cell tumors. Vascular endothelial growth factor may have an important role in metastasis from germ cell tumor. Therefore, there is some rationale for the use of sunitinib in patients with cisplatin refractory germ cell tumors. The authors used cisplatin sensitive and cisplatin refractory germ cell tumor cell lines to evaluate the effect of exposure to sunitinib. With promising in vitro results 33 patients who relapsed after a median of 2 cisplatin containing regimens with measurable disease were entered into a clinical study of 50 mg sunitinib daily for 4 weeks followed by a 2-week break, for a 6-week cycle. Although no unexpected side effects were observed, there was modest clinical response, with 3 partial responses and a median progression-free survival of 2 months. Although there was promising preclinical activity in the cisplatin resistant germ cells, the disappointing clinical responses in these patients suggest that sunitinib as a single agent is unlikely to have a significant role in cisplatin refractory cases. Jerome P. Richie, M.D.
argued that not all port sites need fascial closure. Several cases of port-site hernia, however, have been reported recently with the use of bladeless trocars. This study evaluated the incidence of port-site hernias after robot-assisted radical prostatectomy (RARP) as we routinely closed the fascia of only the midline 12-mm port site. Patients and Methods: From 2006 to 2009, 498 patients with localized prostate cancer underwent RARP. Bladeless dilating trocars were used in all of our patients. Routinely, six ports were used: two 12 mm, three 8 mm, and one 5 mm. Fascial closure was performed only for the midline supraumbilical 12-mm port site. Results: In 498 cases of RARP, there were two port-site hernias (0.4%, 2/498). Both cases occurred at the midline supraumbilical 12-mm camera port site. No hernia developed at nonmidline port sites, including the lateral 12-mm port site. Conclusion: Trocar site hernias after RARP are rare. When bladeless dilating trocars are used, routine closure of fascia of non-midline 12-mm or smaller port sites is not necessary. Splitting the muscle and fascia without cutting likely renders routine closure of fascia unnecessary for nonmidline ports that are ⱕ12 mm. Editorial Comment: With more surgeons performing robot-assisted laparoscopy who have not undergone classic laparoscopy training, it is worth revisiting basic principles of laparoscopy. Although I have heard of anecdotal cases of nonmidline port site hernias, the incidence is incredibly low. In this series of approximately 1,500 nonmidline port sites, of which 1,000 were either 8 or 12 mm ports, not a single hernia was reported using dilating trocars. I also do not routinely close these fascial defects, but if there is any doubt, the surgeon should at least inspect each, and if the index finger can pass through the fascia, then the fascia should be closed. Jeffrey A. Cadeddu, M.D.
Urological Oncology: Testis Cancer and Advances in Oncological Therapy Preclinical and Clinical Activity of Sunitinib in Patients with Cisplatin-Refractory or Multiply Relapsed Germ Cell Tumors: A Canadian Urologic Oncology Group/ German Testicular Cancer Study Group Cooperative Study K. Oechsle, F. Honecker, T. Cheng, F. Mayer, P. Czaykowski, E. Winquist, L. Wood, M. Fenner, S. Glaesener, J. T. Hartmann, K. Chi, C. Bokemeyer and C. Kollmannsberger Division of Oncology, Hematology and Bone Marrow Transplantation, Section of Pneumology, University Medical Centre Eppendorf, Hamburg University, Hamburg, Germany Ann Oncol 2011; 22: 2654 –2660.
Background: The objective of the study was to investigate the activity of sunitinib in a cell line model and subsequently in patients with cisplatin-refractory or multiply relapsed germ cell tumors (GCT). Methods: The effect of sunitinib on cell proliferation in cisplatin-sensitive and cisplatin-refractory GCT cell lines was evaluated after 48-h sunitinib exposure by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide] assay, and IC(50) (concentration that causes 50% inhibition of growth) doses were determined. Sunitinib was subsequently administered at a dose of 50 mg/day for 4 weeks followed by a 2-week break to 33 patients using a Simon two-stage design. Results: Sunitinib demonstrated comparable dose-dependent growth inhibition in cisplatin-sensitive and cisplatinresistant cell lines, with IC(50) between 3.0 and 3.8 M. Patient characteristics were as follows: median of 2 (1– 6) cisplatin-containing regimens; high-dose chemotherapy 67%; late relapse 33%; and cisplatin refractory or absolute cisplatin refractory 54%. Toxic effects included fatigue (39%), anorexia (21%), diarrhea (27%), mucositis (45%), nausea (33%), hand-foot syndrome (12%), dyspepsia (27%), and skin rash (18%). No unexpected side-effects were observed. Thirty-two of 33 patients were
533
534
TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY
assessable for response. Three confirmed partial responses (PRs) and one unconfirmed PR were seen for a total response rate of 13%. Median progression-free survival (PFS) was 2 months, with a 6-month PFS rate of 11%. Conclusions: Sunitinib shows in vitro activity in cisplatin-resistant GCT cell lines. Modest clinical activity in heavily pretreated GCT patients was observed. Editorial Comment: The majority of cases of germ cell tumor are cured with cisplatin based regimens. However, patients who relapse after cisplatin based therapy or high dose chemotherapy have generally a poor prognosis. Various agents have been examined, including single agents such as paclitaxel, gemcitabine, etoposide and oxaliplatin. Different combinations have shown response rates up to 50%, including a 10% long-term survival rate, although generally duration of remission is moderate. Mismatch repair deficiency and microsatellite instability are thought to be associated with cisplatin resistance in human germ cell tumors. Vascular endothelial growth factor may have an important role in metastasis from germ cell tumor. Therefore, there is some rationale for the use of sunitinib in patients with cisplatin refractory germ cell tumors. The authors used cisplatin sensitive and cisplatin refractory germ cell tumor cell lines to evaluate the effect of exposure to sunitinib. With promising in vitro results 33 patients who relapsed after a median of 2 cisplatin containing regimens with measurable disease were entered into a clinical study of 50 mg sunitinib daily for 4 weeks followed by a 2-week break, for a 6-week cycle. Although no unexpected side effects were observed, there was modest clinical response, with 3 partial responses and a median progression-free survival of 2 months. Although there was promising preclinical activity in the cisplatin resistant germ cells, the disappointing clinical responses in these patients suggest that sunitinib as a single agent is unlikely to have a significant role in cisplatin refractory cases. Jerome P. Richie, M.D.