Phase II randomized trial comparing vinorelbine versus vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies

Abstract

BACKGROUND Some previous studies have shown that vinorelbine (VNB) is active in recurrent salivary gland tumors. METHODS Between April 1993 and April 1997, 36 patients in a Phase II randomized trial received either cisplatin, 80 mg/m2, on Day 1 plus VNB, 25 mg/m2, on Days 1 and 8 (every 3 weeks) (for a minimum of 3 cycles (Arm A [16 patients]), or VNB, 30 mg/m2/week, (for a minimum of 9 wks) (Arm B [20 patients]). There were 23 males and 13 females with a median age of 59 years (range, 20–74 years) and a median Eastern Cooperative Oncology Group performance status of 1 (range, 0–2). Four patients had been treated with prior surgery (S) or radiotherapy (RT), 27 patients had been treated with S plus RT, and 5 patients had been treated with S plus RT plus mitoxantrone. Eighteen patients had major salivary gland tumors, and 18 patients had minor salivary gland tumors; 9 patients had adenocarcinoma, 22 patients had adenoid cystic carcinoma, 1 patient had a malignant mixed carcinoma, 3 patients had undifferentiated carcinoma, and 1 patient had a mucoepidermoid carcinoma. The site of recurrence was local in (16 patients), local plus metastatic in 5 patients, and metastatic only in 15 patients. These characteristics were well balanced between the 2 arms. RESULTS In Arms A and B a complete response (CR) was noted in 3 patients (19%) and no patients, respectively; a partial response (PR) was noted in 4 patients (25%) and 4 patients (20%), respectively; no change was noted in 6 patients (37.5%) and 9 patients (45%), respectively; and progressive disease was noted in 3 patients (19%) and 7 patients (35%), respectively. The median duration of the CR was 15+ months (range, 6–27+ months) and for PR the median duration was 7.5 months (range, 3–11+ months) and 6 months (range, 3–9 months) in Arms A and B, respectively. Number of patients surviving > 12 months was 6 versus 1 in Arms A and B, respectively (P < 0.05). Grade 2–3 nausea and emesis was statistically higher (P < 0.001) in Arm A; there was no significant difference with regard to other side‐effects between the two treatment arms. CONCLUSIONS VNB is a drug with moderate activity in salivary gland malignancies. The combination of cisplatin plus VNB was found to be more active than VNB alone, with a good number of CRs and long‐term survivors reported in the current study. Cancer 2001;91:541–7. © 2001 American Cancer Society.

A phase 2 study of platinum and gemcitabine in patients with advanced salivary gland cancer

“…Although it may slightly increase the chance of an objective tumor response, it is not fully clear that combination therapy offers a therapeutic advantage over therapy with single agents that have documented activity, such as mitoxantrone, 13,14 epirubicin, 15 paclitaxel, 16 and vinorelbine. 17 Thus, the choice of a combination regimen, particularly 1 containing cisplatin, must bear in mind the likelihood of additional toxicities. As a single-agent, cisplatin has to our knowledge been evaluated prospectively in only 1 clinical trial 18 ; 2 objective responses were observed in 13 patients with ACC, 1 in 5 patients with MEC, and none in 5 with adenocarcinoma.…”

Schedule-Dependent Interaction between Vinblastine and Cisplatin in Ehrlich Ascites Tumors in Mice

“…Most of these clinical trials showed that the combination of Vinca alkaloids and CDDP did not produce a significant response rate or prolonged survival, and in many cases, increased toxicity was observed (Mulder et al, 1982;Fuks et al, 1983;Newman et al, 1983;Blumenreich et al, 1987;Fraschini et al, 1988). Two recent reports on salivary gland malignancies (Airoldi et al, 2001) and non-small-cell lung cancer (DePas et al, 2001) showed positive results of this schedule.…”

“…Combined chemotherapy schedules including cisplatin [cisdiamminedichloroplatinum(II); CDDP] and various tubulinbinding agents are well established and are used for treatment of various malignancies, such as testicular cancer, lung cancer, and salivary gland, melanoma, and breast carcinomas (Auersperg et al, 1977;Mulder et al, 1982;Fuks et al, 1983;Newman et al, 1983;Huberman et al, 1986;Blumenreich et al, 1987;Creagan et al, 1987;Fraschini et al, 1988;Stefenelli et al, 1988;Haskell, 1990;Kosmidis et al, 1994;Eton et al, 1999;Airoldi et al, 2001;De Pas et al, 2001). Design of currently used combined chemotherapeutic schedules is based on data derived from preclinical studies, and Phase I and II clinical studies.…”

Imatinib in the treatment of solid tumours

“…The response rates of ACC to conventional cytotoxic chemotherapy have been generally modest, and were primarily derived from small institutional series and clinical trials. The objective response rates of ACC to cytotoxic agents such as fluorouracil, anthracyclins, platinum compounds, paclitaxel, and vinorelbine are in the range of 15-30% [129][130][131][132][133][134]. Duration of response to chemotherapy typically is in the range of 6 to 9 months, with some responses lasting in excess of a year.…”