Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations
Purpose: To assess the efficacy and safety of neoadjuvant docetaxel + cisplatin chemotherapy with androgen deprivation therapy for the treatment of locally advanced prostate cancer (PCa) in patients harboring germline DNA damage repair genes (gDDR) defects. Methods: We conducted a prospective observ...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-09-01
|
| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359221128356 |
| _version_ | 1818029413443305472 |
|---|---|
| author | Chenfei Chi Jiazhou Liu Liancheng Fan Yinjie Zhu Yanqing Wang Jianjun Sha Yiran Huang Baijun Dong Jiahua Pan Wei Xue |
| author_facet | Chenfei Chi Jiazhou Liu Liancheng Fan Yinjie Zhu Yanqing Wang Jianjun Sha Yiran Huang Baijun Dong Jiahua Pan Wei Xue |
| author_sort | Chenfei Chi |
| collection | DOAJ |
| description | Purpose: To assess the efficacy and safety of neoadjuvant docetaxel + cisplatin chemotherapy with androgen deprivation therapy for the treatment of locally advanced prostate cancer (PCa) in patients harboring germline DNA damage repair genes (gDDR) defects. Methods: We conducted a prospective observational study in patients with locally advanced PCa confirmed with gDDR defects through next-generation sequencing. All patients received either docetaxel + cisplatin (platinum-group) or docetaxel chemo-hormonal therapy (docetaxel group) followed by radical prostatectomy with extended lymphadenectomy. The primary end point was biochemical progression-free survival (bPFS) and secondary end points include postoperative pathological response and safety assessment during the study period. Results: A total of 36 patients were included in the study, among whom 14 and 22 patients received docetaxel + cisplatin and docetaxel treatment, respectively. Down-staging of Tumor (T), Nodes (N), and Metastasis (M) stages was observed in 11 (78.57%) and 9 (40.9%) patients ( p = 0.041), respectively, in the docetaxel + cisplatin group and docetaxel group. The median bPFS was 7.76 months (95% CI 0.770–14.748) and not reached in the docetaxel group and docetaxel + cisplatin group, respectively. bPFS was significantly longer in the docetaxel + cisplatin group ( p = 0.039) with a hazard ratio of 0.386 (95% CI 0.151–0.987, p < 0.05). Furthermore, one patient discontinued docetaxel + cisplatin after second cycle due to severe liver insufficiency which was confirmed as viral hepatitis A and no significant perioperative complications was observed in either group. Conclusion: This study suggests that cisplatin may increase docetaxel anticancer activity with tolerable safety profile in patients with locally advanced PCa carrying gDDR defects in the neoadjuvant setting, a hypothesis which will require prospective, randomized confirmation. |
| first_indexed | 2024-12-10T05:19:18Z |
| format | Article |
| id | doaj.art-260111f7ee11487c99a3c0314a705562 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-12-10T05:19:18Z |
| publishDate | 2022-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-260111f7ee11487c99a3c0314a7055622022-12-22T02:00:52ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592022-09-011410.1177/17588359221128356Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterationsChenfei ChiJiazhou LiuLiancheng FanYinjie ZhuYanqing WangJianjun ShaYiran HuangBaijun DongJiahua PanWei XuePurpose: To assess the efficacy and safety of neoadjuvant docetaxel + cisplatin chemotherapy with androgen deprivation therapy for the treatment of locally advanced prostate cancer (PCa) in patients harboring germline DNA damage repair genes (gDDR) defects. Methods: We conducted a prospective observational study in patients with locally advanced PCa confirmed with gDDR defects through next-generation sequencing. All patients received either docetaxel + cisplatin (platinum-group) or docetaxel chemo-hormonal therapy (docetaxel group) followed by radical prostatectomy with extended lymphadenectomy. The primary end point was biochemical progression-free survival (bPFS) and secondary end points include postoperative pathological response and safety assessment during the study period. Results: A total of 36 patients were included in the study, among whom 14 and 22 patients received docetaxel + cisplatin and docetaxel treatment, respectively. Down-staging of Tumor (T), Nodes (N), and Metastasis (M) stages was observed in 11 (78.57%) and 9 (40.9%) patients ( p = 0.041), respectively, in the docetaxel + cisplatin group and docetaxel group. The median bPFS was 7.76 months (95% CI 0.770–14.748) and not reached in the docetaxel group and docetaxel + cisplatin group, respectively. bPFS was significantly longer in the docetaxel + cisplatin group ( p = 0.039) with a hazard ratio of 0.386 (95% CI 0.151–0.987, p < 0.05). Furthermore, one patient discontinued docetaxel + cisplatin after second cycle due to severe liver insufficiency which was confirmed as viral hepatitis A and no significant perioperative complications was observed in either group. Conclusion: This study suggests that cisplatin may increase docetaxel anticancer activity with tolerable safety profile in patients with locally advanced PCa carrying gDDR defects in the neoadjuvant setting, a hypothesis which will require prospective, randomized confirmation.https://doi.org/10.1177/17588359221128356 |
| spellingShingle | Chenfei Chi Jiazhou Liu Liancheng Fan Yinjie Zhu Yanqing Wang Jianjun Sha Yiran Huang Baijun Dong Jiahua Pan Wei Xue Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations Therapeutic Advances in Medical Oncology |
| title | Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations |
| title_full | Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations |
| title_fullStr | Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations |
| title_full_unstemmed | Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations |
| title_short | Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations |
| title_sort | efficacy of neoadjuvant docetaxel cisplatin chemo hormonal therapy versus docetaxel chemo hormonal therapy in patients with locally advanced prostate cancer with germline dna damage repair gene alterations |
| url | https://doi.org/10.1177/17588359221128356 |
| work_keys_str_mv | AT chenfeichi efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT jiazhouliu efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT lianchengfan efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT yinjiezhu efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT yanqingwang efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT jianjunsha efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT yiranhuang efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT baijundong efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT jiahuapan efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations AT weixue efficacyofneoadjuvantdocetaxelcisplatinchemohormonaltherapyversusdocetaxelchemohormonaltherapyinpatientswithlocallyadvancedprostatecancerwithgermlinednadamagerepairgenealterations |