422 Abstracts/Lung Cancer 10 (1994) 395-430

mg/m’ day 1. To isolate the effects of dose-intensity versus total dose, the planned cumulative cisplatin dose was 800 mg/nl in each arm. fnrietus and Merhods: Between July 1988 and April 1990, 356 patients were rtnrolled and 323 were eligible and assessable. All patients had metastauc, measurable disease. were chemotherapy-naive, and had a performance status (PS) of 0 to 2. Results: Confirmed complete plus partial response tates were SDCP, 12%; HDCP, 14%: and HDCP-M, 27% (P < .05). Complete responses were uncommon (HDCP. 3%; HDCP-M. 4%) and were observed only in the high-dose arms. Progressive disease occurred more frequently in the SDCP arm (57 46) compared with HDCP (38 %) or HDCP-M (34%) (P < .05). However, there were no significant differences in mediao survival times (SDCP, 6.9 months; HDCP, 5.3 months; HDCP-M, 7.2 months; P = 53). The mean delivered dose-intensity for clsplatio was significantly greater in the high-dose arms: HDCP 41 mglm’lwk and HDCP-M 39 mgim’lwk, versus SDCP 23 mglm’lwk (P = .05). The high-dose arms resulted in an mcreased incidence of ototoxiciry. em&s, and myelosuppression. but similar degm of renal toxicity and oeuropathy compared with SDCP. Conclusion: This study does not confirm evidence of a steep clinical dose-response curve for cisplatm in NSCLC at the cisplauo dose-intensities achieved. The addition of mitomycin increases the response rate, but does not improve survival. Continued evaluation of new agents m thts disease IS warranted.

Cisplatin, S-fluorouracil, and etoposide for advanced non-small cell lung cancer Lynch TJ Jr. Kass F, Kalish LA, Elias AD. Strauss G, Shulman LN et al. Hematology-Oncology Unit. Massachuserts General Hospital, Fruit Street. Boston. MA 02114. Cancer 1993:71:2953-7.

Background. Cisplatin and atoposide combination chemotherapy is the most commonly used regimen for advanced non-small cell lung cancer (NSCLC). S- Fluorouracil(5-FU) IS an agent with little intrinsic activity against NSCLC. However, there is increasing evidence that 5- FU is synergistic with cisplatin and vice versa. In an effort to improve on the traditional chemotherapeutic approach to NSCLC, a treatment regimen consisting of cisplatio. 5-FU, and etoposide (PFE) was developed. Methook. Thirty-five patieocs with advanced NSCLC were treated with the PFE regunen (cisplatin 25/m&&/d and 5-FU loo0 mg/ ml/d by continuous inlits1ooandetoposide60 mg/mz/d, each for4days). Tba cycles were repeated every 28 days. Resufrs. The patients received a mean of 2.8 cycles of PFE. Ten patients had a partial response to chemotherapy for an overall response rate of 28.6%. The median survival was 7.0 months. Toxicities included myocardial infarction (2 of 35), congestive heart failure (2 of 35). fatal pulmonary embolus (1 of 35). and a cerebrovascular accident ( 1 of 35). Toe incidence of Grade 4 oeutropenia (5.7%) and thrombocytopoia (8.5%) was acceptable. Conclurionr. The response rate, duration of response, and survival in this group of 35 patients treated with PFE was similar to that reported for cisplatm and etoposide. The increased cardiovascular toxicity may be the result of the infused 5-FU.

The case for mitomycin in non-small cell lung cancer Spain RC, Hortobadyi GN. Division of Oncology, St. Luke’s Hospital. 1311 Shake Boulevard. Cleveland. 01144104. Oncology (Switzerland) 1993:5O:Suppl. 1:35-52.

The activity of mitomycin in non-small cell lung cancer (NSCLC) has beem well documented in both single-institution pilot and muiti- institution random&d trials. Despite the inclusion of patients ineligible for current trials of newer single agents due to poor performance status, prior umdiatioo to indicator lesions, orpriorchamotberapy, mitomycin emerges from such prior studies as the most consistently active single

agent currently available for NSCLC. While randotnizcxl trials in stage IV disease demonstrate an improved response rate with mitomycin and cisplatin in comparison with cisplatin alone (p = 0.03). and with mitomycin, viodesine, and cisplatin in comparison with vindesine and cisplatin alone (p = 0.003). the potential with mitomycio is most apparent with weekly bolus or infused vindesine/vinblastine, and higher-dose cisplatiu (MVP) in neoadjuvant approaches to stage III disease. Indeed. four trials ofoeoadjuvant MVP m predominantly stage IIIA (bulky N2) disease produced a consistent 1 g-month median and 26- 33 56 3-year survival, which is to be compared with 8 months and 6 56, respectively, with traditional thoracic inadiatioo alone. Nonetheless, priorusc:ofmitomycinwithoutguidelin~forcumulativedose,sch~ulz, or guidelines for use in combined-modality therapy has produced widespread frustration stemming not only from frequent sntioeoplastic effect, but also from frequent toxicity. The several related syndromesof mitomycio-associated thrombotic microangiopathy, ranging from hamolytic-uremic syndrome to pulmonary injury, appear avoidable through limiting the cumulative mttomycin dose to a maximum of 30 mg/m$ scheduling mitomycin at not less than J- to 6-week intervals. perioprativa use of corticosteroids and low inspired oxygen; and close patient follow-up. W&ile daxamethasone preceding mitomycin reduces the frequency and severity of mitomycin-associated lung injury (p = 0.0005). daxamethasooc premedicatmoalso reduces the response rate of MVP in NSCLC (p < 0.025).

Mitomycin, ifosfamide, and cisplatin in non-small cell lung cancer Cullen MH. Queen Elizabeth Hospital. Edgbaston, Birmingham El5 27X. Oncology (Switzerland) 1993:5O:Suppl. 1:31-1.

Mitomycia. ifosfamide, and cisplatin have demonstrated the best single-agent activity thus far in patients with non-smalt ceil lung cancer (NSCLC), the most common malignant disease in the western world. For this reason, we initiated a phase II study. giving these three agents in combination (designated MIC) to 74 patients with inoperable NSCLC. Sixty-stx pauents were evaluable for response. of whom 30 (45%) demonstrated a partial response and 7 ( 11 W) a complete response. These results, along with those obtained in two other phase II trials of MIC in NSCLC. prompted us to begin a large-scale, multicenter, phase III study of MIC in patients with inoperable limited-stage NSCLC. In this oogomg study, patients have been randomized to receive treatment with .MIC and radiotherapy or radiotherapy alone. We hope. to resolve the issue of whether a survival advantage is conferred on NSCLC patients treated with radiotherapy in combination with this promising chemotherapeutic regimen.

Experience with mitomycin in the treatment of non-small ceil lung cancer Folmao RS. Deparzmenr of Medicine. Section of Oncology, Bridgepoti Hospital, Bridgepon. CT Oncology (Switzerland) 1993:5O:SuppI. 1:24-30.

Mitomycin has proven to be among the most active drugs available for the single-agent treatment of non-small cell lung cancer (NSCLC). In combination with vioca alkaloids and cisplatin. mitomycin cart produce response rates greater than or equal to 50% in properly selected patients. In our experience, such responses were achieved using moderate doses (7 or 8 mg/m’) of mitomycin, which also resulted in fewer hematologic and other toxicities. Delivery of MVP (mitomycin/vinca alkaloidlcisplarm) to 150 patients with stages III and IV NSCLC during thelast decadeshowedmaximal respon~wasachievdaftertwoorthrrz cycirsoftherapy. A comparativeanalysisofresultsreported using MVP regimens suggests that high response rates are associated with greater do~-intenslveuseofcisplatinaodIrs~rdose-inteosivellseofrmtomycin.