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A phase I study with Satraplatin and simultaneous chest radiation for non-small cell lung cancer

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DOI: 10.4236/alc.2012.13003    3,289 Downloads   8,761 Views  

ABSTRACT

Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site; 2) previously resected disease with mediastinal relapse; or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Iyengar, P., Hodges, J., Hughes, R., DiMaio, M., Petrone, M., Yun, S. and Choy, H. (2012) A phase I study with Satraplatin and simultaneous chest radiation for non-small cell lung cancer. Advances in Lung Cancer, 1, 13-19. doi: 10.4236/alc.2012.13003.

References

[1] Jemal, A., et al. (2010) Cancer statistics. CA: A Cancer Journal for Clinicians, 60, 277-300. doi:10.3322/caac.20073
[2] Pfister, D.G., et al. (2004) American society of clinical oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. Journal of Clinical Oncology, 22, 330-53. doi:10.1200/JCO.2004.09.053
[3] Lawrence, T., Ten Haken, R. and Giaccia, A. (2008) Principles of radiation oncology. In: De Vita, V., Lawrence, T. and Rosenberg, S., Eds., Cancer: Principles and practice of oncology, 8th Edition, Lippincott Williams and Wilkins, Philadelphia.
[4] Johnson, D.H., et al. (1990) Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non-small cell lung cancer. Annals of Internal Medicine, 113, 33-38.
[5] Joss, R.A., et al. (1984) New agents in non-small cell lung cancer. Cancer Treatment Reviews, 11, 205-236. doi:10.1016/0305-7372(84)90009-4
[6] Furuse, K., et al. (1999) Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. Journal of Clinical Oncology, 17, 2692-2699.
[7] Fournel, P., et al. (2005) Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d’Oncologie thoracique-groupe Francais de pneumo-cancerologie NPC 95-01 study. Journal of Clinical Oncology, 23, 5910-5917. doi:10.1200/JCO.2005.03.070
[8] Curran, W.J. Jr., et al. (2011) Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: Randomized phase III trial RTOG 9410. Journal of the National Cancer Institute, 103, 1452-1460. doi:10.1093/jnci/djr325
[9] Bonomi, P., et al. (2003) Randomized 3-arm phase II study of paclitaxel (T), carboplatin (C), and thoracic radiation (TRT) for patients with stage III non-small cell lung cancer (NSCLC). Report of locally advanced multimodality protocol (LAMP)-ACR 427. Lung Cancer, 41, S77.
[10] Zemanova, M., Petruzelka, L., et al. (2002) Concurrent versus sequential radiochemotherapy with vinorelbine plus cisplatin (V-P) in locally advanced non-small cell lung cancer. A randomized phase II study (abst). Proceedings of the American Society of Clinical Oncology, 21, 290a.
[11] Loehrer, P.J. and Einhorn, L.H. (1984) Drugs five years later cisplatin. Annals of Internal Medicine, 100, 704-713.
[12] Rozencweig, M., et al. (1977) Cis-diamminedichloroplatinum (II). A new anticancer drug. Annals of Internal Medicine, 86, 803-812.
[13] Prestayko, A.W., et al. (1979) Cisplatin (cis-diammine- dichloroplatinum II). Cancer Treatment Reviews, 6, 17-39. doi:10.1016/S0305-7372(79)80057-2
[14] Schaake-Koning, C., et al. (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. The New England Journal of Medicine, 326, 524-530.doi:10.1056/NEJM199202203260805
[15] Gralla, R.J., Cvitkovic, E. and Golbey, R.B. (1979) cis-Dichlorodiammineplatinum(II) in non-small cell carcinoma of the lung. Cancer Treatment Report, 63, 1585-1588.
[16] McKeage, M.J., et al. (1997) Phase I and pharmacokinetic study of an oral platinum complex given daily for 5 days in patients with cancer. Journal of Clinical Oncology, 15, 2691-2700.
[17] Kurata, T., et al. (2000) Pharmacokinetic and pharmaco- dynamic analysis of bis-acetato-ammine-dichlorocyclo-hexylamine-platinum(IV) (JM216) administered once a day for five consecutive days: A phase I study. Japanese Journal of Clinical Oncology, 30, 377-384. doi:10.1093/jjco/hyd102
[18] (2004) Satraplatin, GPC biotech investigator’s brochure.
[19] Twentyman, P.R., et al. (1992) Sensitivity to novel platinum compounds of panels of human lung cancer cell lines with acquired and inherent resistance to cisplatin. Cancer Research, 52, 5674-5680.
[20] Amorino, G.P., et al. (1999) Radiopotentiation by the oral platinum agent, JM216: Role of repair inhibition. International Journal of Radiation Oncology & Biology & Physics, 44, 399-405. doi:10.1016/S0360-3016(99)00033-4
[21] Amorino, G.P., et al. (2000) Combined effects of the orally active cisplatin analog, JM216, and radiation in antitumor therapy. Cancer Chemotherapy and Pharmacology, 46, 423-426. doi:10.1007/s002800000169
[22] Choy, H., Park, C. and Yao, M. (2008) Current status and future prospects for Satraplatin, an oral platinum analogue. Clinical Cancer Research, 14, 1633-1638. doi:10.1158/1078-0432.CCR-07-2176
[23] George, C.M., et al. (2001) A phase I trial of the oral platinum analogue JM216 with concomitant radiotherapy in advanced malignancies of the chest. Investigational New Drugs, 19, 303-310. doi:10.1023/A:1010653508700
[24] Cmelak, A.J., et al. (1999) Phase I study of JM-216 with con-current radiation in non-small cell lung cancer and squamous cell head and neck cancer (abstr). Proceedings of the American Society of Clinical Oncology, 18, 393a.
[25] Brookmeyer, R. and Crowley, J. (1982) A confidence interval for the median survival time. Biometrics, 38, 29-41. doi:10.2307/2530286
[26] Bartelink, H. (1988) Combined modality treatment for primary tumor. National Cancer Institute Monograph, 1988, 247-251.
[27] Steel, G.G. (1988) The search for therapeutic gain in the combination of radiotherapy and chemotherapy. Radiotherapy & Oncology, 11, 31-53. doi:10.1016/0167-8140(88)90044-8
[28] Dillman, R.O., et al. (1990) A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. The New England Journal of Medicine, 323, 940-845. doi:10.1056/NEJM199010043231403
[29] Sause, W., et al. (2000) Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation therapy oncology group, eastern cooperative oncology group, and southwest oncology group. Chest, 117, 358-364. doi:10.1378/chest.117.2.358
[30] Klastersky, J., et al. (1989) Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. Lung cancer working party, Belgium. Journal of Clinical Oncology, 7, 1087-1092.
[31] Wozniak, A.J., et al. (1998) Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: A southwest on- cology group study. Journal of Clinical Oncology, 16, 2459-2465.
[32] Dillman, R.O., et al. (1996) Improved survival in stage III non-small-cell lung cancer: Seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. Journal of the National Cancer Institute, 88, 1210-1215. doi:10.1093/jnci/88.17.1210
[33] Sause, W.T., et al. (1995) Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: Preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. Journal of the National Cancer Institute, 87, 198-205. doi:10.1093/jnci/87.3.198
[34] Sorensen, J.B., Clerici, M. and Hansen, H.H. (1988) Single-agent chemotherapy for advanced adenocarcinoma of the lung. A review. Cancer Chemotherapy and Pharma- cology, 21, 89-102. doi:10.1007/BF00257354
[35] Bartelink, H., et al. (1988) Combined treatment with radiation and anticancer drugs: Experimental and clinical results. In: Bartelink, H., Ed., Radiobiology in Radiotherapy, Springer-Verlag, London, 177-179.
[36] Begg, A., Stewart, F. and Dewit, L. (1987) Interactions between cisplatin and radiation in experimental rodent tumors and normal tissues. Antitumor drug-radiation interactions. CRC Press, Boca Raton, 154-170.
[37] Douple, E.B. and Richmond, R.C. (1979) Radiosensitization of hypoxic tumor cells by cis- and trans-dichlorodiammineplatinum (II). International Journal of Radiation Oncology & Biology & Physics, 5, 1369-1372. doi:10.1016/0360-3016(79)90672-2
[38] Von der Maase, H., Overgaard, J. and Vaeth, M. (1986) Effect of cancer chemotherapeutic drugs on radiation- induced lung damage in mice. Radiotherapy & Oncology, 5, 245-257. doi:10.1016/S0167-8140(86)80054-8
[39] Bartelink, H., et al. (1986) Therapeutic enhancement in mice by clinically relevant dose and fractionation schedules of cis-diamminedichloroplatinum (II) and irradiation. Radiotherapy & Oncology, 6, 61-74. doi:10.1016/S0167-8140(86)80110-4
[40] Lelieveld, P., et al. (1985) The effect of treatment in frac- tionated schedules with the combination of X-irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin. International Journal of Radiation Oncology & Biology & Physics, 11, 111-121. doi:10.1016/0360-3016(85)90369-4
[41] Tanabe, M., Godat, D. and Kallman, R.F. (1987) Effects of fractionated schedules of irradiation combined with cis-diamminedichloroplatinum II on the SCCVII/St tumor and normal tissues of the C3H/KM mouse. International Journal of Radiation Oncology & Biology & Physics, 13, 1523-1532. doi:10.1016/0360-3016(87)90320-8
[42] Begg, A.C., Bohlken, S. and Bartelink, H. (1989) The effect of cisplatin on the repair of radiation damage in RIF1 mouse tumours in vivo. Radiotherapy & Oncology, 15, 79-91. doi:10.1016/0167-8140(89)90121-7
[43] Squibb, B.-M. (1998) Phase I study of oral bis (acetato) amine dichloro cyclohexylamine platinum (IV) (Satraplatin, JM-216) given daily x 5 (CA142-003/CA142-009). Bristol-Myers Squibb Interim Safety Report Accession No. 9100663081998.
[44] Squibb, B.-M. (1999) Phase I/II study with JM-216 and simultaneous radiation in locally advanced non-small cell lung and head and neck cancer (CA142-020), 1999.

  
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