Front‐line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma

Abstract

BACKGROUND The conventional treatment of brain metastases not amenable to surgery is most often radiotherapy. Until now, pharmacologic issues related to the blood brain barrier (BBB) prevented a wide evaluation of chemotherapy. The authors previously reported that the combination of cisplatin (P) and etoposide (E) had strikingly high activity in patients with brain metastases from breast carcinoma. The purpose of this study was to assess, in a larger prospective study, the front‐line activity of that combination against brain metastases from breast carcinoma (BC), nonsmall cell lung carcinoma (NSCLC), and malignant melanoma (MM) in patients previously untreated with radiotherapy. METHODS From December 1986 to July 1993, 116 patients received P 100 mg/m2 on Day 1 and E 100 mg/m2 on Days 1, 3, and 5 or on Days 4, 6, and 8 every 3 weeks. An insignificant change in the E schedule using the same dose on a random basis assured the prospective enrollment and the registration of all cases. Six patients were not eligible and three patients were excluded from the analysis because they were lost to follow‐up shortly after the date of registration. One‐hundred seven patients were considered for analysis. The distribution according to the primary tumor site was BC in 56 patients (52%), NSCLC in 43 (40%), and MM in 8 (8%). The first evaluation of response was performed after two cycles. In cases of no disease progression, chemotherapy was continued to a maximum of six cycles. RESULTS Among the 56 patients with BC, 7 achieved complete response (CR) (13%), 14 achieved partial response (PR), 12 had no change (NC), 15 had progressive disease (PD), and 8 had insufficient treatment or response was not assessed. The CR plus rate was 38%. Among the 43 patients with NSCLC, 3 achieved CR (7%), 10 achieved PR, 15 had SD, 7 had PD, and 8 had insufficient treatment or response was not assessed. The CR plus PR rate was 30%. None of the eight patients with MM achieved an objective response. The median survival was 31 weeks for patients with BC (range, 0–287), 32 for patients with NSCLC (0–392+), and 17 for patients with MM (2–48). CONCLUSIONS The combination of P and E is effective for patients with brain metastases from BC and NSCLC. In this study, the response rate was of the same order as that reported for disseminated disease without central nervous system involvement. The survival figures compare favorably with some others reported in the literature for patients given radiotherapy. A randomized study is warranted to compare this chemotherapy followed by radiotherapy with radiotherapy alone for patients with brain metastases from BC or NSCLC not amenable to surgery or radiosurgery. Cancer 1999;85:1599–605. © 1999 American Cancer Society.

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: Phase II study

“…The role of chemotherapy in patients with BrM by NSCLC is still controversial. However, among patients with NSCLC and BrM, response to different chemotherapy regimens, such cisplatin-gemcitabine or cisplatin-ifosfamide-irinotecan, was similar to that achieved in other disease sites [3][4][5][6][7][8][9]. Instead, for patients with recurrent or persistent BrM after WBRT and at least one line of chemotherapy, the treatment options available are limited.…”

“…Whole brain radiotherapy (WBRT) improves neurological symptoms in about 50% of patients and lengthens the median survival from 3 to 6 months [2]. Recent trials suggest that epipodophillotoxins alone or combined with cisplatin are very effective in treating NSCLCrelated BrM and ifosfamide-mitomycin-cisplatin or gemcitabine-cisplatin combinations have been evaluated with similar good responses [3][4][5][6][7][8][9]. Temozolomide (TMZ) is a novel, oral, alkylating agent with virtually 100% bioavailability [10][11][12].…”

Emlőtumor intracranialis metasztázisainak eredményes szisztémás palliatív kemoterápiája

“…Szolid daganatok cerebralis metasztázisainak kezelé-sében néhány szisztémásan adott kemoterápiás szer hatásosságáról rendelkezésünkre állnak eseti beszámolók (1. táblázat) [1,5]. Randomizált, kontrollált vizsgálatok ebben a betegcsoportban nem történtek [3], és a speciá-lis helyzetre való tekintettel nem is számíthatunk rá, hogy a közeljövőben ilyen vizsgálatokat végezzenek.…”

“…Randomizált, kontrollált vizsgálatok ebben a betegcsoportban nem történtek [3], és a speciá-lis helyzetre való tekintettel nem is számíthatunk rá, hogy a közeljövőben ilyen vizsgálatokat végezzenek. Egy prospektív vizsgálatban a cisplatin-etoposid kombináció agyi áttétes emlődaganatos betegek 38%-ánál, nem kissejtes tüdődaganatos betegek 30%-ánál biztosított parciális vagy komplett remissziót [5]. Randomizált vizsgála-tok hiányában az esetbemutatások is felértékelődnek.…”

“…A kemoterápianaiv betegnél olyan szisztémás kemoterá-piás kombinációt kellett választanunk, amely a vér-agy gáton a lehető legnagyobb valószínűséggel jut át. Az irodalomban a legtöbb, vér-agy gáton történő bejutást alá-támasztó adat az alkilálószerekkel és az etoposiddal kapcsolatban gyűlt össze [1,5]. A hazai kemoterápiás gyűjteményben nem szereplő ifosfamid-etoposid kombinációt a fellelhető irodalom és korábbi személyes tapasztalatok alapján választottuk.…”