cisplatin and etoposide (vp-16) as a single regimen for small cell lung cancer. a phase ii trial
Embed Size (px)
Characterizationofahnmansmallcelllnngcarcinomacelllinewith acquired resistance to cis-diamminedichloroplatinum(ID in vitro. Hospars GAP, Mulder NH, De Jong B et al. Division of Medical OncologyDepartmen~ ofInternal Medicine, University Hospital, 9713 EZ Groningen. Cancer Res 1988;48:6803-7.
A 6.4-fold cis-diamminedichloroplatinum(11) (CDDP) resistant humansmallcelllungcarcinomacellline(GLC,-CDDP)wasdeveloped to study acquired CDDP resistance in vitro. Compared to the sensitive cell line (GLC& the GLC,-CDDP showed an increase in doubling time and a decrease in cloning efficiency, cellular size, double minutes per cell, cellular protein, and nuclear protein content. While a complete cross-resistance for wraplatin and a partial cross-resistance for doxom- bicin, melphalan, cadmium chloride, carboplatin, and cis-dichloro- trans-dihydroxo-cis-bis(isoprolylamine)platinum(lV) (resistance fac- tor, respectively, 220.127.116.11.2.1, 18.104.22.168) was found, no cross-resistance for vincristine was found. In the GLC,-CDDP line in comparison to the GLC, line, glutathione and total amount of sulfhydryl compounds was significantly increased, whileglutatbione S-transferaseandglutathione reductase was the same. The platinum content in cells and nuclei was lower in the resistant line, but after correction for cellular protein or volumenodifference was found. Theamountof platinum bound to DNA was significantly lower in the GLC,-CDDP line. After a 1 -h incubation with CDDP, the amount of Pt-GG adducts was the same and tbe amount of interstrand cross-links was reduced in the GLC,-CDDP line as compared to GLC,. In conclusion, in the GLC,-CDDP line the pheno- type and genotype are changed and various mechanisms, such as decreased P&DNA binding, elevated glutathione, and reduced inter- strand cross-links, play a role in the development of the CDDP resis- tance.
Results of a iive-drug combination chemotherapy in non-small cell lung cancer. A phase II trial. Marechal F, lncatasciato C, Cattan A. Institut Jean-Godinot. Medical Oncology Departmenr, F-51056 Reims Cedex. Acta Oncol 1988; 27537-9.
Twenty-six non-small lung cancer patients entered a phase II trial of a 5-drug combination chemotherapy. On day 1, patients received vinblastine, bleomycin, metbotrexate, 5-FU, cisplatiuum, leucovorin, and a similar sequence with an increased dosage was administered on day 6. Out of 22 fully evaluable patients we observed 1 CR and 7 PR. Hematological toxicity was significant, including IS cases of neu- tropenia grade 4 and four grade 3, with one death during aplasia. Our results are disappointing but they are similar to most current reports on drug combinations in advanced non-small cell lung cancer. A better scheduling might improve the efficiency toxicity ratio.
High dose chemotherapy with autologous bone marrow rescue in small cell lung cancer. Wilson C, Pickering D, Stewart S et al. Depnrtmen~ of Clinical Oncol- ogy, MRC Leubemio Unir. Royal Postgroduare Medical School, Hammersmi~h Hospital, London W12 OHS. In Vivo 1988;2:331-4.
Twenty five patients diagnosed as having small cell lung cancer (SCLC) were treated with etoposide and cisplatinum. After assessment for tumour response, autologous bone marrow (ABM) was collected from fivepatients ingoodclinicalstatewhohadshownapartialresponse (PR)andnobonemarrowinvolvementwithtumour.Thesepatientswere treated with high dose cisplatinum, etoposide and melphalan and then by ABM infusion. Although all patients (3 with extensive and 2 with limited disease) responded (4 CR and 1 PR), 3 patients with extensive disease relapsed and died of their disease. One patient with limited disease died of infection while pancytopaenic; one patient is alive but has relapsed at eighteen months. Although patient numbers are small, our data support the conclusion that high dose chemotherapy and autologous bone marrow rescue has a very small role or none at all in the management of patients with extensive or limited stage SCLC.
Continuation of chemotherapy versus supportive care alone in patients with inoperable non-small cell lung cancer and stable disease after two or three cycles of MACC. Results of a randomized prospective study. Buccheri GF, Ferrigno D, Curcio A, Vola F, Rosso A. Medical Deporr-
menf. A. Carle Hospital of Chest Diseases. 12100 Cuneo. Cancer 1989;63:428-32.
Recommendations concerning the continuation of chemotherapy in nonresponding patients with non-small cell lung cancer (NSLCL) and stable disease after the first chemotherapy test are empirical and often conflicting. Between 1984 and 1987,116 inoperable NSCLC patients were treated with methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC regimen). After two or three cycles of therapy, 74 patientswerejudgedlohavestablediseaseandassignedatmndomeither tochemotherapy maintenance with the same regimen (38 subjects) or to chemotherapydiscontinuation(36subjecls).Thetwostudygroupswere comparableforall tbemajorprognostic factors. Median time toprogres- sion was 26 weeks for the chemotherapy group compared to 24 weeks for the nonchemotherapy group (P = NS). Median survival was pro- longed in the treatment arm (47 weeks) compared to the nontreatment arm (30 weeks), which was statistically significant. A patient self- assessment of thequality of life revealed a significantly worse tolerance to therapy and a better physical condition in the chemotherapy group. Objective MACC toxicity was significant with two treatment-related deaths. This study failed to demonstrate sufficient therapeutic benefits to justify the increased cost and toxicity of continuing treatment in nonresponding NSCLC patients.
Cisplatin and etoposide (VP-16) as a single regimen for small cell lung cancer. A phase II trial. Boni C, Cocconi G, Bisagni G, Ceci G, Peracchia G. Servizro di Oncologic& Ospedale Maggiore, 431W Parma. Cancer 1989:63:638- 42.
Forty-seven consecutive patients with small cell lung cancer (SCLC) were treated with a combination chemotherapy program including 60 mg/m’ of cisplatin (P) on day 1 and 120 mg/m’of etoposide Q on day 4,6,8,every21 days.Limiteddisease(LD)patients,achievingcomplete response (CR) or partial response (PR) after the three initial courses, received radiotherapy (RT) to the pretreatment primary tumor volume and, those achieving CR, additional RT to the brain. During RT, chemotherapy was administered with 50% dose reduction. Forty-three patients were evaluable for therapeutic response. In the 19 patients with LD, CR was achieved in 63% of patients and the PR rate was 32%. In 24 patients with extensive disease (ED), CR was 34% and PR rate was 54%. Median duration of survival was 66 weeks for LD and 48 weeks for ED. Six patients were disease-free after 2 years. Leucocyte count <2fKO/mm’ was seen in 26% of patients; platelet count cSCHX0/mm3 was observed in 9%. Nonhematologic toxicity included universal nausea or vomiting and severe neurotoxicity in 7%. These data indicate that PE combination is a very active front-line regimen in SCLC and could be suggested as one of the reference treatments.
The influence of chemotherapy on plasma coagulation and fibrinol- ytic systems in lung cancer patients. Ruiz MA, Marugan I, Estelles A et al. Deparrrneru ofHemalology and Oncology. UniversiQ Clinic Hospilal, Valencia 46010. Cancer 1989;63:643-8.
After the administration of cytostatic drugs, an increase in throm- bcembolic phenomena has been described in cancer patients. The authors studied the changes in plasmatic coagulation and tibrinolysis in ~0patientswithnonopembleSmgelllandIVlungcanceraftercytosmtic chemotherapy. The results show significant postchemotherapy in- creases in fibrinopeptide A levels, as well as a decrease in fibrinolytic activity reflected by a drop in functional tissue activator. Also the authors studied the potential accumulative effect of threechemotherapy cycles. A significant increase in functional plasminogen activator inhibitor has been noted. Chemotherapy is apparently capable of conditioning a decrease in tibrinolytic activity in these cancer patients that could be related to the enhanced tendency to developing throm- boembolic phenomena after cytostatic chemotherapy.
Differential response to treatment with the bis(ethyl)polyamine analogues between human small cell lung carcinoma and undiffer- entiated large cell lung carcinoma in culture. Casero RA, Jr. Ervin SJ, Celano P, Baylin SB, Bergeron RJ. Johns Hopkins Oncology Center. Johns Hopkins Universiry School of Medi-