Response Rate Of Brain Metastases Research Articles

Efficacy of pembrolizumab in patients with brain metastasis caused by previously untreated non-small cell lung cancer with high tumor PD-L1 expression

ObjectivesPembrolizumab is recommended for patients with previously untreated non-small cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥1%. The KEYNOTE-024 study described the efficacy of pembrolizumab in patients with previously untreated NSCLC who had a PD-L1 TPS of at least 50 %. However, patients with untreated brain metastasis (BM) were excluded from many clinical trials. Therefore, we assessed the efficacy of pembrolizumab against BM of NSCLC with high tumor PD-L1 expression. Materials and MethodsWe retrospectively reviewed patients who received pembrolizumab as first-line treatment against NSCLC with PD-L1 TPS ≥ 50 % between March 2017 and September 2019. Treatment efficacy was compared between patients with (BM group) and without BM (non-BM group). In addition, the BM group was divided into patients who previously received treatment for BM before pembrolizumab (BM-T group) and those with no prior treatment for BM (BM-not T group). ResultsEighty-seven patients (23 BM group and 64 non-BM group) were assessable for efficacy. No significant differences in patient characteristics were found between the BM and non-BM groups, but proportion of patients with stage IV at diagnosis was significantly higher in the BM group. Median progression-free survival (PFS) (6.5 months vs. 7.0 months) and overall survival (OS) (21.6 months vs. 24.6 months) did not significantly differ between the two groups. The response rate of BM was 70 %. The BM group was subdivided into 13 patients in the BM-T group and 10 patients in the BM-not T group. No significant differences in patient characteristics were found between the two groups, but maximum diameter of BM and proportion of patients with symptomatic BM were significantly greater in the BM-T group. PFS and OS did not significantly differ between the two groups. The median PFS of BM was 13.6 months in the BM-T group and 18.6 months in the BM-not T group. ConclusionPembrolizumab may be effective for BM caused by previously untreated NSCLC with high PD-L1 tumor expression.

A phase II study of osimertinib for patients with radiotherapy-naïve CNS metastasis of non-small cell lung cancer harboring EGFR mutations: The OCEAN study (LOGIK 1603/WJOG 9116L).

9597 Background: Approximately 15%–30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression. Although radiotherapy is a standard treatment for CNS metastasis, the efficacy of radiotherapy against CNS is poor. The aim of OCEAN study was to assess the efficacy of osimertinib for patients with radiotherapy-naïve CNS metastasis of NSCLC harboring EGFR mutations. Methods: OCEAN study was two-cohort phase II trial, 65 patients (T790M cohort; 40 patients and first-line cohort; 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive NSCLC was included. Patients were treated with osimertinib 80 mg once daily. The primary endpoint was the response rate of brain metastasis (BMRR) assessed by the PAREXEL criteria. We set a threshold value of 50% and an expected value of 70% based on the overall response rate (ORR) of AURA trial. Based on one-sided alpha = 0.05 and power = 0.8, the sample size of T790M cohort was calculated to be 40. Key secondary endpoints were progression-free survival (PFS), and ORR, BMRR assessed by the RECIST criteria. We are exploratorily assessing the blood concentration of osimertinib at day 22, which considered to represent steady state. In this report, we present the results of T790M cohort. Results: Between October 2016 to July 2019, 40 participants were recruited in the T790M cohort. The median age was 66.5 with 30.0% male. Eight patients had symptomatic CNS metastasis and most patient had multiple CNS metastasis (77.5%). BMRR assessed by PAREXEL criteria was 66.7% (95%CI: 54.3 – 79.1%) and BMRR assessed by RECIST was 70.0% (95%CI, 49.9 – 90.1%). Median PFS was 7.1 months (95%CI, 3.4 – 13.6 months) and ORR assessed by RECIST was 40.5% (95%CI, 24.7 – 57.9%). Treatment related pneumonitis was observed in 4 patients (10.0%). There was no grade 3 or higher toxicities that were found in more than 10%. Conclusions: This first study assessed the efficacy of osimertinib for patients with radiotherapy-naïve CNS metastasis of EGFR T790M mutation-positive NSCLC. The OCEAN study met primary endpoint. The results of this study suggested that patients with brain metastasis harboring EGFR T790M mutations had better to receive osimertinib prior to brain radiotherapy. Clinical trial information: 071180017 .

A phase II study of Osimertinib for patients with radiotherapy-na\xefve CNS metastasis of non-small cell lung cancer: treatment rationale and protocol design of the OCEAN study (LOGIK 1603/WJOG 9116L)

BackgroundPatients with activating epidermal growth factor receptor (EGFR) mutations are highly responsive to EGFR-tyrosine kinase inhibitors (TKIs). However, it has been reported that approximately 15–30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression, and patients with EGFR mutations exhibit a higher incidence of brain metastasis than those without such mutations. The efficacy of osimertinib for treating CNS metastasis has been reported, but its efficacy for CNS metastasis in radiotherapy-naïve patients is unclear.MethodsIn the present prospective two-cohort phase II trial, 65 patients (T790M cohort, 40 patients; first-line cohort, 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive non-small cell lung cancer (NSCLC) will be included. Patients will be treated once-daily with osimertinib 80 mg. The primary endpoint is the response rate of brain metastasis as assessed using the PAREXEL criteria. Key secondary endpoints are progression-free survival and the response rate of brain metastasis as assessed using the RECIST criteria. We will exploratorily analyze the relationships of the blood concentration of osimertinib with its efficacy against brain metastasis of NSCLC and the accumulation of osimertinib in cerebrospinal fluid and evaluate tumor-derived DNA from plasma specimens for mutations in EGFR and other genes. Recruitment, which in October 2016, is ongoing.DiscussionAlthough previous reports revealed the efficacy of osimertinib for CNS metastasis, these reports only involved subgroup analysis, and the efficacy of osimertinib for patients with previously untreated CNS metastasis remains unclear. The OCEAN study is the only trial of osimertinib for patients with untreated brain metastasis of NSCLC. This study should provide novel data about osimertinib. If the results of the OCEAN study are positive, then avoidance of radiotherapy will be recommended to patients harboring EGFR mutations and brain metastasis.Trial registrationUMIN identifier: UMIN000024218 (date of initial registration: 29 September 2016). jRCT identifier: jRCTs071180017 (date of initial registration: 13 February 2019).

MTE26.02 EGFR Targeted Therapies: Lessons Learned

MTE26.02 EGFR Targeted Therapies: Lessons Learned

Abstract P6-17-09: Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients

Abstract Background: Breast cancer remains the second leading cause of CNS metastases. HER2 positive and triple negative subtypes are especially and independently at higher risk of developing brain metastases. Although surgical resection and radiosurgery may play a role in the management of selected cases, whole brain radiation therapy remains the standard treatment but with limited efficacy. Temozolomide (TMZ); an oral alkylating agent that cross the blood brain barrier has shown radiosensitizing characteristics as well as synergistic effects of radiation therapy (RT). The aim of the study was to assess the efficacy and safety of WBRT with concomitant TMZ in treatment of brain metastases in breast cancer patients. Patients and methods: A prospective randomized study included 60 patients with newly diagnosed brain metastases (BMs) from breast cancer not candidate for surgical resection or radiosurgery. All patients received WBRT 30 Gy/10 fractions with or without TMZ, administered at a dosage of 75 mg/m2/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment defined as partial response (PR) or complete response (CR) on brain MRI (WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurological symptoms and tolerability. Results: Between October 2011 and October 2013, 60 patients were enrolled in the study, 30 patients received WBRT+TMZ (group A) and 30 patients received WBRT (group B). Median age was 54 years (30-65), median follow up was 10.4 months (3-36). ORR was 80% in the WBRT+TMZ arm versus 50% in the WBRT (p = 0.017). The median PFS were 11.8 versus 5.8 respectively (p = 0.005). The median OS was 13.8 for group A and 10.8 for group B (p = 0.59). WBRT+TMZ was well tolerated with mostly grade 2 non-hematologic toxicity; headache, nausea & vomiting were 6%, 15% & 12% in group A versus 12%, 9% & 6% in group B, respectively. While the most evident hematologic toxicity recorded was lymphopenia grade 2 & 3 (15% & 12% in group A) and (12% & 9% in group B). No grade 4 toxicities were noted. Conclusion: WBRT plus TMZ improve local control and response rate of BMs from breast cancer, which was reflected by improved PFS. Citation Format: El-Sadda WM, Abdel-Halim II, El-Ibrashi MM, Magdi MM. Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-09.

Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis.

ObjectiveThe aim of the present meta-analysis is to evaluate the response rate, median survival time (MST) and toxicity in patients with brain metastases (BM) originating from non-small cell lung cancer (NSCLC) and who were treated using either whole brain radiotherapy (WBRT) plus concurrent chemotherapy or WBRT alone.MethodsPubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.ResultsIn total, six randomized controlled trials (RCT) involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019) than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST) (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233) or time of neurological progression (CNS-TTP) (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543), and increased adverse events (Grade≥3) (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000). There were no significant differences in Grade 3–5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92).ConclusionThe combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.

Pemetrexed and cisplatin combination with concurrent whole brain radiotherapy in patients with brain metastases of lung adenocarcinoma: a single-arm phase II clinical trial

Pemetrexed-based chemotherapy presented about 40 % response rate (RR) on brain lesions of non-small cell lung cancer (NSCLC). But whole brain radiotherapy (WBRT) is still the standard treatment when surgery or radio-surgery is not feasible. This trial evaluated the efficacy and safety and efficacy of pemetrexed-cisplatin plus concurrent WBRT in this population. Forty-two patients were enrolled this study. Patients with newly diagnosed NSCLC with brain metastasis (BM) and performance status (PS) 0-2 were eligible for WBRT. Patients received up to six cycles of cisplatin and pemetrexed (75 and 500 mg/m(2), respectively) every 3 weeks. On day 1-12 during the first cycle of chemotherapy, patients received WBRT 30 Gy/10 fx/12 days. Primary end point was objective RR and progression free survival (PFS) on BM. Secondary end points included extracerebral and overall RR, survival and safety profile. Forty-one were evaluable for response. The histology was all adenocarcinoma. The objective cerebral RR (complete and partial response) in the intent-to-treat population was 68.3 % (28 of 41 patients). Extracerebral and overall RR was 34.1 and 36.6 %, respectively. Progression free survival of BM was 10.6 months, and median overall survival was 12.6 months. The combined treatment with pemetrexed-cisplatin and concurrent WBRT are effective in patients with NSCLC with newly diagnosed BM. This modality of treatment appears to be particularly favorable in RR and progression free survival of BM. Further clinical studies are warranted.

Irinotecan and carboplatin for treatment of brain metastases from small-cell lung cancer

19032 Background: Brain metastasis occurs commonly in patients with small-cell lung cancer (SCLC). Herein we report the efficacy of irinotecan and carboplatin in the treatment of brain metastases from SCLC. In addition, we review the existing data on chemotherapy for brain metastases in SCLC. Methods: Eighty patients with metastatic or relapsed SCLC were enrolled in a phase II trial of irinotecan and carboplatin according to a 2-stage design. Chemonaive patients were treated with irinotecan 200 mg/m2 and carboplatin AUC of 5; whereas chemotherapy-treated patients received irinotecan 150 mg/m2 and carboplatin AUC of 5, every 21 days for 6 cycles. Results: The most common grade III/IV toxicity included neutropenia (50%), anemia (11%), thrombocytopenia (19%), diarrhea (20%) and nausea/emesis (11%). Among the 80 patients, 15 (19%) presented with brain metastases. An analysis of 14 assessable patients with brain metastases revealed an overall response rate of 65% after 2 cycles of chemotherapy, and a median survival of 6 months (1 to 24 months). Upon review of the literature, 8 studies were identified with more than 10 patients who had received chemotherapy for brain metastases from SCLC. Based on these studies, the response rate of brain metastases from SCLC to a variety of chemotherapy ranged from 22 to 85% and median survival of patients ranged from 3 to 9 months. Conclusion: Chemotherapy, including the regimen of irinotecan and carboplatin, is an effective treatment for brain metastases from SCLC. (Supported by Pfizer, Inc. and NCI K24CA10014) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer, Inc.

Response of Intracranial Metastases to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: It May All Depend on EGFR Mutations

TO THE EDITOR: We read with great interest the case description by Fekrazad and colleagues in the Journal. They describe a nonsmoking Native American woman with brain metastases from a lung adenocarcinoma who had a marked response to monotherapy with erlotinib at 150 mg/d. Although they do not provide these data, it is very likely that the patient had an activating epidermal growth factor receptor (EGFR) mutation, based on her clinical characteristics and response to the oral tyrosine kinase inhibitor (TKI) erlotinib. In the recently reported phase II trials of gefitinib 250 mg/d and erlotinib 150 mg/d for patients with the L858R and exon 19 deletion EGFR mutations, patients with CNS metastases were included. The overall response rate in these and other prospective trials of gefitinib and erlotinib exceed or equal 75% for all sites. In both instances, it seems that patients with intracranial metastases also have a similar high level of tumor responses in their CNS. The Spanish Lung Cancer Group followed the CNS response of seven chemotherapynaivepatients with an EGFR mutation given erlotinib 150 mg/d (available as part of the 2006 ASCO Annual Meeting’s slide presentation of their abstract). They reported four patients with a complete response and three with a partial response to this EGFR inhibitor: a 100% response rate of brain metastases. These results are astounding, and indicate that in a molecularly selected population with brain metastases, both gefitinib and erlotinib can achieve high response rates in a metastatic site that historically has not been sensitive to systemic chemotherapeutic agents used in non–small-cell lung cancer. Despite the striking efficacy of these EGFR inhibitors, secondary resistance is common and the brain may actually be the first site of loss of response to EGFR TKIs. Others have speculated that over time the effective dose of gefitinib in the CNS may wean to levels that are subtherapeutic to inhibit EGFR mutations. We look forward to mature results of prospective trials that evaluate the clinical benefit of EGFR TKIs in patients who have EGFR mutations with brain metastases. It is not inconceivable to think that in this patient population, oral TKIs may replace or supplement radiation therapy for management of brain metastases.

Chemotherapy for Brain Metastases in Small-Cell Lung Cancer

PURPOSEBrain metastasis occurs commonly in patients with small-cell lung cancer (SCLC). Herein, we report the efficacy of irinotecan and carboplatin in the treatment of brain metastases from SCLC. In addition, we review the existing data on chemotherapy for brain metastases in SCLC. PATIENTS AND METHODSEighty patients with metastatic or relapsed SCLC were enrolled in a phase II trial of irinotecan and carboplatin. Patients naive to chemotherapy were treated with irinotecan 200 mg/m2 and carboplatin AUC of 5, and patients previously treated with chemotherapy received irinotecan 150 mg/m2 and carboplatin AUC of 5, every 21 days for 6 cycles. RESULTSAmong the 80 patients, 15 (19%) presented with brain metastases. An analysis of 14 assessable patients with brain metastases revealed an overall response rate of 65% after 2 cycles of chemotherapy and a median survival of 6 months (range, 1-24 months). Upon review of the literature, 8 studies were identified as having > 10 patients who received chemotherapy for brain metastases from SCLC. Based on these studies, the response rate of brain metastases from SCLC to a variety of chemotherapy and median survival of patients ranged from 22% to 85% and 3 months to 9 months, respectively. CONCLUSIONChemotherapy, including the regimen of irinotecan and carboplatin, is an effective treatment for SCLC brain metastases.

Superiority of bi-dimensional measurements compared to RECIST in measuring response of metastatic brain tumors

1542 Background: Criteria for measuring response rates of brain metastases are not well established. Unilateral (RECIST), and bilateral (WHO) criteria were developed to approximate tumor volume, which is the gold standard but difficult to measure. We compared WHO and RECIST criteria to volumetrics in patients with metastatic breast cancer lesions in the brain treated with lapatinib. Methods: MRI data from 20 patients enrolled in a prospective phase II study at UNC-Chapel Hill, the Dana-Farber/Harvard Cancer Center, and Georgetown were retrospectively analyzed. Post-gadolinium MRI images were analyzed at baseline and at 2 month intervals over a 7 month period. 196 lesions were analyzed for tumor size using one-dimensional (single greatest diameter), bidimensional (product of 2 longest diameters in perpendicular dimensions), and volume (calculated with an institutionally-derived software program) measurements. Tumor response was classified according to WHO and RECIST criteria. Progressive disease required a >20% increase, partial response >30% decrease, and stable disease for those in between. Similar definitions for volume measurements were used. Results: 3 of 20 patients were excluded as the diffuse metastatic nature of their tumors and small size prevented application of the RECIST or WHO measurement criteria. RECIST correctly predicted volumetric response or progression in 12/17 cases, but was delayed by either one or two scan cycles in reaching that conclusion in 3 of these 12 cases. WHO criteria correlated with volumetrics in 16/17 cases with a delay of one scan interval in a single case. The delay in correct identification of response category was particularly noticeable in identifying progressive disease with RECIST as compared to volumetrics. RECIST was only 50% specific for progressive disease at the time that progression was documented with volume. WHO was 90% specific. Both methods were sensitive to clinical benefit (SD + PR) (RECIST 86%; WHO 100%). Conclusions: For metastatic brain tumors that are large enough to be measured with linear criteria, WHO bidimensional criteria appear superior to unidimensional RECIST measurements in predicting volumetric response of tumors. Supported by EB000219-NIBIB and UNC Breast SPORE CA58223. No significant financial relationships to disclose.

Response of Asymptomatic Brain Metastases From Small-Cell Lung Cancer to Systemic First-Line Chemotherapy

The purpose of this study was to investigate the radiologic response of asymptomatic brain metastases (BM) from small-cell lung cancer (SCLC) to first-line systemic chemotherapy. From 1990 to 2003, 181 consecutive patients with SCLC were enrolled onto this study. Patients were examined by a neurologist on a regular basis. Magnetic resonance imaging (MRI) of the brain was performed routinely before (at diagnosis of SCLC) and after first-line systemic chemotherapy. Patients were treated with combination chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Clinically manifest BM were treated with whole-brain radiotherapy (WBRT). The response rate (RR) of BM was assessed by changes in the size or the number of enhanced lesions on MRI using standard criteria. Synchronous asymptomatic BM were found in 24 SCLC patients (13%). In six (27%) of the 22 assessable patients, the asymptomatic BM responded to systemic chemotherapy. A systemic response was found in 16 patients (73%). All patients became symptomatic during follow-up. The symptom-free survival did not differ between cranial responders and cranial nonresponders. The RR of asymptomatic BM from SCLC to systemic chemotherapy is 27% and evidently lower than the systemic RR. Future studies should focus on the possible beneficial effect of WBRT for patients with asymptomatic synchronous BM.

Management of brain metastases.

Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3-3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligible; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated.

The diagnosis and management of brain metastases.

The median survival after whole-brain irradiation of patients with brain metastases is 4 months. Because half the patients with brain metastases die of systemic cancer, for most the benefit of intensive local treatment (surgery or stereotactic radiosurgery) of brain metastases will be minimal. In particular, patients with controlled systemic disease and one to three brain metastases are candidates for intensive local treatments. Combined local treatment with whole-brain irradiation therapy improves the local control of brain metastases in comparison with whole-brain irradiation only. After the local treatment of brain metastases by either surgery or radiosurgery, overall survival is not adversely affected if whole-brain irradiation is only administered as salvage treatment at the time of relapse. New randomized trials are needed, however, to investigate this further. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumour and non-cerebral metastases.

Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer

Twenty-three patients with brain metastases from non-small cell lung cancer (NSCLC) (median age 62 years, Karnofsky PS 50-100) were treated with cisplatin (100 mg/m 2, day 1) and teniposide (80 mg/m 2, days 1, 3 and 5) every 3 weeks. Response was evaluated by contrast-enhanced brain CT every two to three cycles of treatment. The objective response rate of brain metastases was 35% (8/23); three patients achieved complete response (CR) and five partial response (PR). The median response duration was 24 weeks for CR patients and 32 weeks for PR patients. The median survival was 21 weeks overall and 45 weeks for responding patients. Grade 3/4 leukocytopenia and thrombocytopenia were seen in 28 and 9%, respectively. Two patients died from infections while in neutropenia. Cisplatin and teniposide seems an active regimen against brain metastases in NSCLC. These data may indicate the need for reconsideration of the role of chemotherapy for brain metastases of NSCLC.

Systemic chemotherapy for brain metastasis from small cell lung cancer

Small cell lung cancer (SCLC) is rapidly progressive, but is sensitive to chemotherapy. The incidence of brain metastasis is high in patients with this disease. The management of brain metastases is an important problem in SCLC patients, because brain tumors have been regarded as being inaccessible to anti-cancer agents due to the blood-brain-barrier (BBB). Of 15 SCLC patients with brain metastasis at diagnosis who were treated with chemotherapy, 3 achieved a complete response (CR) and 4 had a partial response (PR), giving a response rate of 47%. Of 17 SCLC patients with brain metastasis at relapse, 1 achieved a CR and 6 had a PR by chemotherapy, with a response rate of 30%. The response rate of brain metastasis in SCLC patients treated with chemotherapy was similar to those of primary lesions and other metastatic lesions. SCLC patients with brain metastasis at diagnosis had the same response rate and median survival time as other ED-SCLC patient. The BBB may not be an impending factor in systemic chemotherapy of brain metastasis in SCLC. Systemic chemotherapy may be the treatment of choice for SCLC patients with brain metastasis.