Phase II study of concurrent temozolomide and whole brain radiation therapy in patients with brain metastasis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1540-1540 ◽  
Author(s):  
S. Dawood ◽  
J. Ragaz ◽  
S. Navaratnam ◽  
C. Mihalcioiu
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Median Survival ◽  
Systemic Disease ◽  
Performance Status ◽  
Single Agent ◽  
End Points ◽  
Status Score ◽  
Moderate Nausea ◽  
Single Agent Chemotherapy

1540 Background: 30% of patients (pts) with lung cancer develop brain metastases, with XRT representing the conventional treatment of multiple BM. Methods: Pts with lung cancer, Brain metastases (BM) and performance status of 0–2 were enrolled. TMZ (75mg/m2 day 1–14) given on cycle 1 with XRT (3000cGy in 10 fractions) followed by cycles 2–4 TMZ (200mg/m2 day 1–5, q 4 weeks). Pts with active systemic disease received also chemotherapy (cisplatin or docetaxel or paclitaxel) during TMZ cycles 2–4. Primary end points: 1. Radiological response of BM assessed after 4–6 weeks from the end of XRT, 2. Treatment related toxicity, 3.Functional Scale score(FSS)(1 best, 3 worst, based on interaction of WHO performance status, score 0–4, with the neurological status score 1–3). FSS was assessed at baseline, and during the follow up visits. Secondary end points: time to progression and overall survival. Results: 22 patients enrolled, 8 pts received TMZ alone and 14 pts had additional chemotherapy. CR was documented in 2 pts, PR in 6 pts, SD in 5 pts, 4 pts progressed on treatment; 5 pts were not evaluable (death from other causes within 2 months from diagnoses). FSS at baseline was available on 19/22 patients. Of those, thirteen, four and two pts had a FSS of 1, 2 and 3, respectively. Fifteen of the 19 pts maintained their FSS at the end of Tx, with 3 pts exhibiting deterioration, and one patient improved. Post treatment FSS remained stable in 16 patients up to one month prior to death. The median survival (22 pts) from the time of diagnosis of BM was 9 months with average TTP of 3.5 months. Except for moderate nausea and vomiting there was no significant toxicity by combining TMZ with XRT. The addition of single agent chemotherapy to TMZ was well tolerated but two patients who required GCSF support. Conclusion: Adding TMZ to XRT for the treatment of BM from in lung cancer patients showed a response in 13 out of 17 assessable patients with a median survival of 9 months which is above the mean 3 to 6 months survival reported in the literature with XRT alone. More importantly, the majority of patients maintained a stable FSS up to one month prior to death suggesting a quality of life benefit during most of their life span. TMZ can be safely administered concomitantly with either XRT or with other single agent chemotherapy. No significant financial relationships to disclose.

scholarly journals Survival of patients with synchronous brain metastases: an epidemiological study in southeastern Michigan

2000 ◽  
Vol 9 (2) ◽  
pp. 1-5 ◽  
Author(s):  
Ajith J. Thomas ◽  
Jack P. Rock ◽  
Christine C. Johnson ◽  
Linda Weiss ◽  
Gordon Jacobsen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Median Survival ◽  
Cancer Diagnosis ◽  
Systemic Disease ◽  
Primary Source ◽  
Primary Site ◽  
Unknown Primary ◽  
Primary Cancer ◽  
Significant Difference ◽  
Frequent Site

Object It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring greater than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents. Methods Data obtained in 2682 patients with synchronous brain metastases treated from 1973 to 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median survival length was 3.3 months. There was no significant difference in the median survival in patients with primary lung/bronchus and those with an unknown primary site (3.2 months and 3.4 months, respectively). Conclusions Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in greater than 90% of cases, is related to systemic disease; however, despite poor median survival lengths, certain patients will experience prolonged survival.

scholarly journals 418 Phase 1b/2 KEYNOTE-365 cohort I: platinum-containing chemotherapy alone or in combination with pembrolizumab for treatment-emergent neuroendocrine prostate carcinoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A448-A448
Author(s):  
Johann De Bono ◽  
Neal Shore ◽  
Gero Kramer ◽  
Anthony Joshua ◽  
Xin Tong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Carcinoma ◽  
Response Rate ◽  
Performance Status ◽  
Ecog Performance Status ◽  
End Points ◽  
Status Score ◽  
Modified Recist ◽  
Phase 1B ◽  
Performance Status Score

BackgroundTreatment-emergent neuroendocrine prostate carcinoma (t-NE) can occur de novo or after diagnosis of prostate adenocarcinoma. Treatment often includes platinum-containing chemotherapy because of t-NE’s histologic similarity to small cell lung cancer. The PD-1 inhibitor pembrolizumab has shown promising efficacy and acceptable safety when combined with olaparib, docetaxel, or enzalutamide for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the multicohort phase 1b/2 KEYNOTE-365 study (NCT02861573). Cohort I will be used to compare platinum-containing chemotherapy alone with chemotherapy + pembrolizumab as treatment for t-NE.MethodsPatients who have t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review); experienced progression within 6 months of starting a next-generation hormonal agent (NHA) for mCRPC or hormone-sensitive prostate cancer and experienced progression within 6 cycles of docetaxel treatment for mCRPC; and have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 are eligible. Prior therapy with ≤2 NHAs and 1 other chemotherapy for mCRPC is permitted. Patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg IV on day 1 of each cycle every 3 weeks + carboplatin AUC of 5 IV on day 1 + etoposide 100 mg/m2 IV on days 1, 2, and 3 of each 21-day cycle for 4 cycles (arm 1) or the same chemotherapy regimen without pembrolizumab (arm 2); in each arm 40–100 patients will be enrolled. Pembrolizumab treatment will continue up to 2 years until disease progression, unacceptable toxicity, or withdrawal of consent. Patients will be stratified by ECOG performance status score (0 or 1). Computed tomography or magnetic resonance imaging will be performed every 9 weeks through week 54 and every 12 weeks thereafter. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are time to PSA progression; ORR and radiographic progression-free survival (PFS) per PCWG3-modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 by BICR and PCWG3-modified RECIST v1.1 by BICR; and overall survival. End points will be summarized for each arm without formal hypothesis testing.AcknowledgementsMedical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicaltrials.gov, NCT02861573Ethics ApprovalThe study and the protocol were approved by the Institutional Review Board or ethics committee at each site.

Phase II Trial of Paclitaxel Plus Gemcitabine in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

2001 ◽  
Vol 19 (4) ◽  
pp. 1071-1077 ◽  
Author(s):  
Dolores Isla ◽  
Rafael Rosell ◽  
José J. Sánchez ◽  
Alfredo Carrato ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Median Survival ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Small Cell ◽  
Stage Iiib ◽  
Small Cell Lung ◽  
A Performance

PURPOSE: Given the cisplatin-related myelotoxicity and nonhematologic toxicities, we were prompted to undertake a study of the noncisplatin combination of paclitaxel plus gemcitabine to evaluate the efficacy, tolerance, and survival of this combination in patients with locally advanced and metastatic non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received gemcitabine 2,000 mg/m2 and paclitaxel 150 mg/m2 on days 1 and 15 of a 28-day cycle, for a maximum of eight cycles. RESULTS: Between December 1997 and June 1998, 89 untreated NSCLC patients were enrolled; 30 (34%) had stage IIIB disease (23 with malignant pleural effusion and seven without), and 59 (66%) had stage IV disease. Eighty-six percent of patients had a performance status of 0 or 1. The median number of cycles administered was four (range, one to eight cycles). The mean dose-intensity for both paclitaxel and gemcitabine was nearly 100%. Hematologic and nonhematologic toxicities were mild. Thirty-eight patients received second-line chemotherapy after completion of the study. The overall intent-to-treat response rate was 32.2%, with a higher response rate for stage IIIB patients (43.3%) than for stage IV patients (26.3%). Overall median survival was 9.9 months, and 1-year survival was 38.8% (14.2 months for stage IIIB and 7.7 months for stage IV; P = .007). Median survival was 10.2 months for patients with a performance status of 0 or 1 and 4.8 months for patients with a performance status of 2 (P = .007). CONCLUSION: A biweekly paclitaxel/gemcitabine regimen was well tolerated, with an acceptable response rate and a reasonable median survival time, especially in patients with good performance status. It merits further exploration in future studies.

scholarly journals Bevacizumab with Single-agent Chemotherapy in Previously Treated Non-squamous Non-small-cell Lung Cancer: Phase II Study

In Vivo ◽  
2018 ◽  
Vol 32 (5) ◽  
pp. 1155-1160 ◽  
Author(s):  
KAKUHIRO YAMAGUCHI ◽  
TAKESHI MASUDA ◽  
KAZUNORI FUJITAKA ◽  
KEI MIWATA ◽  
SHINJIRO SAKAMOTO ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Previously Treated ◽  
Single Agent Chemotherapy

Phase I trial of tirapazamine in combination with cisplatin in a single dose every 3 weeks in patients with solid tumors.

1997 ◽  
Vol 15 (2) ◽  
pp. 773-780 ◽  
Author(s):  
C A Johnson ◽  
D Kilpatrick ◽  
R von Roemeling ◽  
C Langer ◽  
M A Graham ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Performance Status ◽  
Single Agent ◽  
Maximum Plasma ◽  
Time Curve ◽  
Minor Response ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
A Minor

PURPOSE AND METHODS Tirapazamine (SR4233, WIN 59075) is a benzotriazine-di-N-oxide bioreductive agent that is selectively activated to a reactive DNA-damaging species in hypoxic tumors. Preclinical studies show that synergistic antitumor activity results from a schedule-dependent interaction between tirapazamine and several cytotoxic drug classes, including cisplatin. In a phase I combination study, tirapazamine (130 to 260 mg/m2) was administered as a 1-hour intravenous (IV) infusion beginning 3 hours before cisplatin (75 to 100 mg/m2). Thirteen patients received 41 courses of therapy. These patients had an excellent performance status and were not heavily pretreated. The predominant diagnosis was lung cancer. RESULTS The major acute side effects were nausea and vomiting, which were controlled with an intensive antiemetic regimen. Other acute effects included diarrhea and muscle cramping, while with repeated dosing, anorexia and fatigue predominated. Full doses of each agent were well tolerated in combination, although in this previously treated population, fatigue increased markedly after three cycles of therapy. Partial responses were observed in two patients (one with non-small-cell lung cancer and one with breast cancer), and a minor response occurred in a patient with mesothelioma. Tirapazamine pharmacokinetics were linear with respect to increasing dose with a mean maximum plasma concentration (Cmax) of 5.97 +/- 2.25 microg/mL and an area under the concentration-time curve (AUC) of 811.4 +/- 311.9 microg/mL.min at 260 mg/m2. These results are consistent with other ongoing single-agent and combination studies and indicate that therapeutically relevant levels of tirapazamine are achievable in patients based on animal models. The mean cisplatin AUC was 285.6 +/- 46.4 microg/mL.min with mean Cmax values of 3.38 +/- 0.43 microg/mL at 75 mg/m2. The clearance of cisplatin was unaffected by coadministration with tirapazamine. CONCLUSION This trial shows that in previously treated patients, full doses of cisplatin are well tolerated with increasing doses of tirapazamine up to 260 mg/m2. The observation of clinical responses in this trial supports the phase II investigation of this regimen.

scholarly journals Factors influencing the outcome of stereotactic radiosurgery in patients with five or more brain metastases

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
E. Hamel-Perreault ◽  
D. Mathieu ◽  
L. Masson-Cote
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Nonsmall Cell Lung Cancer ◽  
Factors Influencing ◽  
Treatment Volume ◽  
Extracranial Disease

Background Stereotactic radiosurgery (srs) for patients with 5 or more brain metastases (bmets) is a matter of debate. We report our results with that approach and the factors influencing outcome.Methods In the 103 patients who underwent srs for the treatment of 5 or more bmets, primary histology was nonsmall- cell lung cancer (57% of patients). All patients were grouped by Karnofsky performance status and recursive partitioning analysis (rpa) classification. In our cohort, 72% of patients had uncontrolled extracranial disease, and 28% had stable or responding systemic disease. Previous irradiation for 1–4 bmets had been given to 56 patients (54%). The mean number of treated bmets was 7 (range: 5–19), and the median cumulative bmets volume was 2 cm3 (range: 0.06–28 cm3).Results Multivariate analyses showed that stable extracranial disease (p < 0.001) and rpa (p = 0.022) were independent prognostic factors for overall survival (os). Moreover, a cumulative treated bmets volume of less than 6 cm3 (adjusted hazard ratio: 2.54; p = 0.006; 95% confidence interval: 1.30 to 4.99) was associated with better os. The total number of bmets had no effect on survival (p = 0.206). No variable was found to be predictive of local control. The rpa was significant (p = 0.027) in terms of distant recurrence.Conclusions Our study suggests that srs is a reasonable option for the management of patients with 5 or more bmets, especially with a cumulative treatment volume of less than 6 cm3.

Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery ◽  
2017 ◽  
Vol 83 (1) ◽  
pp. 128-136 ◽  
Author(s):  
E Emily Bennett ◽  
Michael A Vogelbaum ◽  
Gene H Barnett ◽  
Lilyana Angelov ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Early Death ◽  
Tumor Type ◽  
Prognostic Groups ◽  
Prior Surgery

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. OBJECTIVE To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. METHODS A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. RESULTS Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable. CONCLUSION Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.

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