[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results

Abstract Background [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods In total, 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR 8–14 months). The primary outcome endpoint was response assessment according to the visual analogue score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky performance status, overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results In total, 40 patients (15 males and 25 females) with a mean age of 46.6 ± 15.08 years (range 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal, and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty-eight patients died and the estimated median overall survival was 13 months (95% CI 10–14 months). A significant improvement was observed in the VAS, AS, and ECOG status when compared to baseline. None of the patients experienced grade III/IV haematological, kidney, or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

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[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results

10.21203/rs.3.rs-43709/v2 ◽

2020 ◽

Author(s):

Madhav Prasad Yadav ◽

Sanjana Ballal ◽

Marian Meckel ◽

Frank Roesch ◽

Chandrashekhar Bal

Keyword(s):

Overall Survival ◽

Pain Assessment ◽

Bone Pain ◽

Performance Status ◽

Response Assessment ◽

Assessment Criteria ◽

Skeletal Metastases ◽

Efficacy And Safety ◽

Pain Palliation ◽

Global Pain

Abstract Background: [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy is limited. In this light, the objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods: 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3 - 2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR: 8 - 14 months). The primary outcome endpoint was response assessment according to the visual analog score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky Performance Status (KPS), overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results: 40 patients, 15 males, and 25 females with a mean age of 46.6 ± 15.08 years (range: 24 - 78 years) were treated with either 1 (N=15) or 2 (N= 2lobal5) cycles of [177Lu]Lu-DOTA-ZOL. g According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty eight patients died and the estimated median overall survival was 13 months (95% CI: 10 - 14 months). A significant improvement was observed in the VAS, AS and ECOG status when compared to baseline. None of the patients experienced grade III/IV hematological, kidney or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion: [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

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[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results

10.21203/rs.3.rs-43709/v3 ◽

2020 ◽

Author(s):

Madhav Prasad Yadav ◽

Sanjana Ballal ◽

Marian Meckel ◽

Frank Roesch ◽

Chandrashekhar Bal

Keyword(s):

Overall Survival ◽

Pain Assessment ◽

Bone Pain ◽

Performance Status ◽

Response Assessment ◽

Assessment Criteria ◽

Skeletal Metastases ◽

Efficacy And Safety ◽

Pain Palliation ◽

Global Pain

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[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results

10.21203/rs.3.rs-43709/v1 ◽

2020 ◽

Author(s):

Madhav Prasad Yadav ◽

Sanjana Ballal ◽

Marian Meckel ◽

Frank Roesch ◽

Chandrashekhar Bal

Keyword(s):

Overall Survival ◽

Bone Pain ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Response Assessment ◽

Assessment Criteria ◽

Skeletal Metastases ◽

Efficacy And Safety ◽

Pain Palliation ◽

Bone Pain Palliation

Abstract Background: [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy is limited. In this light, the objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers.Methods: 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR: 8–14 months). The primary outcome endpoint was response assessment according to the visual analog score (VAS). Secondary endpoints included analgesic score (AS), global assessment pain score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky Performance Status (KPS), overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0.Results: 40 patients, 15 males, and 25 females with a mean age of 46.6 ± 15.08 years (range: 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty eight patients died and the estimated median overall survival was 13 months (95% CI: 10–14 months). A significant improvement was observed in the VAS, AS and ECOG status when compared to baseline. None of the patients experienced grade III/IV hematological, kidney or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy.Conclusion: [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

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Randomized study of docetaxel (D) and dexamethasone (DX) with low or high dose estramustine (E) for patients with advanced hormone-refractory prostate cancer (HRPC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4653 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4653-4653

Author(s):

T. Nelius ◽

T. Klatte ◽

F. Reiher ◽

S. Filleur ◽

R. Yap ◽

...

Keyword(s):

Overall Survival ◽

Side Effects ◽

Bone Pain ◽

Performance Status ◽

Univariate Analysis ◽

Total Daily Dose ◽

High Dose ◽

Ecog Performance Status ◽

Significant Difference ◽

Psa Response

4653 Background: D-based chemotherapy is a burgeoning option for men with advanced HRPC. Alone or in combination with E, D has been shown to improve median survival. In this study we tested the combination of D with two different doses of E in patients (pts) with HRPC to improve response rates and to lower side effects. Methods: 72 metastatic HRPC pts were randomly assigned to receive D (70 mg/m2 IV, d2, q3w) and E (3 × 280 mg/d PO starting 1 day prior to D, for 5 consecutive days) for arm A or E (3 x 140 mg/d PO starting 1 day prior to D, for 3 consecutive days) for arm B. Premedication with oral DX at a total daily dose of 16 mg, in divided doses two times a day was administered in arm A on day 1 to 5 and in arm B on day 1 to 3. Initially, 6 cycles were administered and repeated after significant PSA rise. Pts were monitored for PSA response, time to progression (TTP), survival and toxicity. Results: PSA declines of ≥75%, ≥50% and ≤50% were 36.8%, 55.3% and 44.7% in arm A and 38.2%, 67.6% and 32.4% in arm B, respectively (P = .442). TTP in Arm A and Arm B were 11 months (95% CI, 7–14) versus 14 months (95% CI, 8–19), P = .6911) and overall survival 21 months (95% CI, 6–35) versus 22 months (95% CI, 18–27), respectively, (P = .4149). The primary treatment-related side effects observed in arm A and arm B were granulocytopenia (34% and 29%, P = .663) and thrombotic complications caused by E (four pts (11%) and one pt (3%), respectively, P = .206). Associated baseline factors with overall survival in univariate analysis were ECOG performance status (P < .001), hemoglobin level (P < .001), bone pain (P < .001), and PSA (P < .097) and in multivariate analysis ECOG performance status (95% CI, 2.9–13.9) and bone pain (95% CI, 3.2–20.1), (P < .001). Conclusions: In this randomized phase II study the combination of D and E had substantial activity in HRPC. We did not find a statistically significant difference of higher dose of E in combination with D compared to a lower dose of E and D regarding PSA response, TTP and survival. However, there was a tendency of higher toxicity in the high dose E group. These treatment-related toxicities were mainly hematologic and manageable. The results of this study support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. No significant financial relationships to disclose.

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Phase 2 Study of a High Dose of 186Re-HEDP for Bone Pain Palliation in Patients with Widespread Skeletal Metastases

Journal of Nuclear Medicine Technology ◽

10.2967/jnmt.113.124297 ◽

2013 ◽

Vol 41 (3) ◽

pp. 192-196 ◽

Cited By ~ 11

Author(s):

E. Pirayesh ◽

M. Amoui ◽

H. R. Mirzaee ◽

F. Tabei ◽

A. Rakhsha ◽

...

Keyword(s):

Bone Pain ◽

Skeletal Metastases ◽

High Dose ◽

Phase 2 ◽

Pain Palliation ◽

Bone Pain Palliation ◽

Phase 2 Study

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Efficacy and safety of regorafenib versus dinutuximab with chemotherapy in Chinese children with neuroblastoma

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v14i1.38807 ◽

2019 ◽

Vol 14 (1) ◽

pp. 32-35

Author(s):

Kun Dong ◽

Guan Wang ◽

Zeng Liang Wang ◽

Xueyan Wang

Keyword(s):

Overall Survival ◽

Supportive Care ◽

Progression Free Survival ◽

Response Assessment ◽

Best Supportive Care ◽

Hazard Ratio ◽

Chinese Children ◽

Efficacy And Safety ◽

Free Survival ◽

To Receive

The objective of the present study was to evaluate the efficacy and safety of regorafenib in comparison with dinutuximab with chemotherapy in Chinese children with advanced neuroblastoma. The patients aged less than 16 years who were histologically diagnosed with advanced neuroblastoma were enrolled and randomized to receive either regorafenib plus best supportive care or dinutuximab plus chemotherapy plus best supportive care in a 1:1 ratio. The tumor response assessment was made in accordance with modified international neuroblastoma response criteria. Adverse events were also assessed. Regorafenib showed prolonged overall survival and progression-free survival than who received dinutuximab plus chemotherapy (overall survival: median 32.3 months versus 27.2 months; hazard ratio = 0.45; 95% CI 0.11-0.13, p<0.001; progression-free survival: stratified hazard ratio = 0.48; 95% CI 0.11-0.14; p<0.01). Moreover, the overall response rate was greater in patients treated with regorafenib as compared to dinutuximab group. Regorafenib appears efficacious and has a manageable safety profile in Chinese children with advanced neuroblastoma.

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A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.354 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 354-354

Author(s):

Eiichiro Suzuki ◽

Shuichi Kaneko ◽

Takuji Okusaka ◽

Masafumi Ikeda ◽

Kensei Yamaguchi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Performance Status ◽

Objective Response ◽

Japanese Patients ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

Class A ◽

Pugh Class ◽

Grade 3

354 Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.

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Abstract No. 378 Association of response to transarterial chemoembolization with overall survival in Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma: comparison of different response assessment criteria

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2019.12.439 ◽

2020 ◽

Vol 31 (3) ◽

pp. S171

Author(s):

W. Xu ◽

P. Tao ◽

J. Wu ◽

M. Yu ◽

M. Soulen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Cancer ◽

Transarterial Chemoembolization ◽

Response Assessment ◽

Barcelona Clinic Liver Cancer ◽

Assessment Criteria ◽

Cancer Stage ◽

Different Response

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Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: a retrospective observational study

Tumori Journal ◽

10.1177/0300891620926244 ◽

2020 ◽

pp. 030089162092624 ◽

Cited By ~ 1

Author(s):

François Cavaille ◽

Mathieu Peretti ◽

Marie Eve Garcia ◽

Roch Giorgi ◽

Nathalie Ausias ◽

...

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Performance Status ◽

Univariate Analysis ◽

Real Life ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung ◽

Effective Treatment Option ◽

Multiple Tumor

Background: Pembrolizumab, a humanized immunoglobulin monoclonal antibody directed against the programmed cell death 1 receptor, demonstrated robust efficacy and a manageable safety profile across multiple tumor types in clinical trials. Aim: To investigate the efficacy and safety of first-line pembrolizumab for patients with non-small cell lung cancers (NSCLCs) in clinical practice. Methods: In this observational monocentric retrospective study, 38 patients with PD-L1 >50% were enrolled between November 2017 and November 2018. Results: The global median overall survival was 11.08 months (95% confidence interval [CI], 5.98–not reached) and the global median progression-free survival was 6 months (95% CI, 3–not reached). In the univariate analysis, clinical performance status score and the development of immune-related adverse events were the only 2 clinical factors significantly correlated with overall survival. Conclusion: The results of the present study suggest that pembrolizumab seems less effective in the real-life population than in the pivotal clinical trials in patients with NSCLC but remains an effective treatment option for patients with NSCLC. Longer follow-up is needed.

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Efficacy and safety of nivolumab for advanced gastric cancer patients with poor performance statuses

10.21203/rs.3.rs-21197/v1 ◽

2020 ◽

Author(s):

Toshihiko Matsumoto ◽

Yosuke Yamamoto ◽

Yusuke Kurioka ◽

Ukyo Okazaki ◽

Shogo Kimura ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Performance Status ◽

Poor Performance ◽

Poor Performance Status ◽

Efficacy And Safety ◽

The Poor ◽

Good Group ◽

Poor Group

Abstract Background: Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcomes compared to best supportive care among AGC patients who received at least two prior regimens. However, there are no reliable data regarding AGC patients with poor performance status (PS) who received nivolumab. We investigated the efficacy and safety of nivolumab among AGC patients with poor PS. Methods: We retrospectively collected clinicopathologic data from patients with AGC who underwent nivolumab monotherapy at our institution from October 2017 to June 2019. Results: Forty-nine AGC patients who received nivolumab were assessed. Twenty-seven patients had PS 0 or 1 (Good group) and 22 had PS 2 or 3 (Poor group). The median progression-free survival and overall survival durations were 61 and 180 days in the Good group, respectively, and 36 and 85 days in the Poor group, respectively. The overall survival was significantly shorter in the Poor group (180 vs 85 days, p =0.0255). The disease control rates were 23% and 9% in the Good and Poor groups, respectively. Thirty-three percent of patients experienced immune-related adverse events in the Good group, and 18% in the Poor group. Conclusion: Nivolumab has a modest effect and is feasible as third- or later-line treatment for AGC patients.

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