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Phase 1b Clinical Trial and Pharmacokinetic Evaluation of Recombinant Human Granulocyte - Macrophage Colony
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Jae Kyung Roh, Jin Hyuk Choi, Hyung Keun Roh, Sun Young Rha, Kyung Hee Lee, Hye Ran Lee, Jee Sook Hahn, Pum Soo Kim, Byung Soo Kim
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J Korean Cancer Assoc. 1994;26(3):495-510.
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 Abstract
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- To define the clinical safeties and hematologic effects of subcutaneously administered yeast- derived recombinant human granulocyte-macrophage colony stimulatina factor(rh GM-CSF, LBD-005h and to determine the maximally tolerated dose(MTD) and the pharmacokinetics. Sngle arm open non-randomized phase Ib study was carried in 15 cancer patients#(14 patients evaluable) with chemotherapy induced bone marrow depression. Rh GM-CSF by once-daily subcutaneous administration to groups of 3-6 patients at doses of 50, 100, 150, 250, 350, 500, 700 ug/m/d for 10 consecutive days was escalated unless greater than WHO grade III toxicites were observed. Intrapatient dose escalation was permitted. Clinical safeties and toxicities were observed with frequent hematologic monitering. Blood and urine were collected on day 1, and 8 of rh GM-CSF administration to evaluate the parmacokinetic parameters. Of the 15 enrolled patients, 14 patients were evaluable. Male to female ratio was 8: 6 with median age 32 y-o(10~70 y-o). Seven patients had osteosarcoma, 2 malignant lymphoma, 2 gastric carcinoma, 2 lung cancer and 1 had uterine leiomyosarcoma. The total administered cycles of rh GM-CSF were 24. At each dose step, 3 patients were treated with exception of 6 patients at 500 ug/m/d dose. At all the doses administered, fever and flue-like syndrome were common side effects. Grade I fever and flue-like syndrome 50~150 pg/m dose, and grade II fever flue- like syndrome were observed at the dose of grater than 250 u/m(2)/d dose. Even at the 700 ug/m(2)/ d dose, no greater than grade III toxicities were observed. Leucocytosis were dose dependent with 120-480% increment of baseline. Pharmacokinetic parameters are as follows; Cmax were dose dependent(0.42-11.7 ng/ml) with 2-4 hours of Tmax. AUC were also dose dependent(3.93~87.9ng.hr/ml) with sustained serum levels(0.2-2ng/ml) up to 12 hours after rh GM-CSF administration. Urinary excretion(0-24 hours) after GM-CSF was less than 1% of administered dose. Yeast-derived rh GM-CSF induces leucocytosis in the dose range of 150~500ug/m(2)/d with tolerable side effects. Subcutaneously administered rh GM-CSF has sustained serum levels up to 12 hours after administration. The doses of 150-500 ug/m/d would be appropriated for the further trials.
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Efficacy of Combined Modality , Multidisciplinary Treatment ( Neoadjuvant Chemotherapy , Difinite Local Treatment , and Adjuvant Chemotherapy ) in Locally Advanced Head and Neck Squamous Cell Carcinoma
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Jae Kyung Roh, Wha Young Lee, Hyun Cheol Chung, Young Joon Park, Hyung Keun Roh, Chang Ok Suh, Gwi Eon Kim, Jun Kyu Loh, Won Pyo Hong, Cheong Soo Park, Byung Soo Kim
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J Korean Cancer Assoc. 1990;22(3):518-532.
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Abstract
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- Between January, 1986 and October, 1989, 40 patients with previously untreated, locally advanced head and neck squamous cell carcinoma enrolled for combined modality treatment (CMT) with neoadjuvant chemotherapy (2 cycles of infusional 5-FU and cis-platin), definite local treatment (DLT) (surgery and/or radiotheray) and adjuvant chemotherapy (3 cycles of infusional 5-FU and cis-platin) to enhance the therpeutic efficacy. Of the 40 enrolled, all the patients were evaluable for tumor responses and treatmen#t related toxicities after neoadjuvant chemotherapy, and 35 patients finished scheduled CMT. Male to female ratio were 33:7, median age 54 year old (34-69), and median ECOG performance grade 1 (0-2). Primary sites were nasopharynx 19, oral cavity 16, larynx 3, hypopharynx 1, and maxillary sinus l. After the 2 cycles of neoadjuvnt therpay, 8/40 (20%), 23/40 (72.5%) achieved compIete remission (CR) and partial remission (PR), respectively with 92.5% over all response rates. After the DLT, 23/ 35 (67.5%) 11/35 (31.4%) achieved CR, and PR respectively with 97.1% over all response rates. Of the 35 patients who finished the DLT, 15 received the 3 cycles of adjuvnat chemotherapy with infusional 5-FU and cis-platin. The median failure-free, and overal survival duration of 35 evaluable patients were 21.7 months and 31.0 months, respectively after the CMT. The median survival duration was significantly prolonged in patients with objective respanses after the neoadjuvant chemotherapy compared to those of non-responders (p<0.05). Of the 35 patients who finished the DLT, patients who received the adjuvant chemotherapy showed trend of prolongation of survival when compared to no adjuvant chemotherapy patients Imedian overall survival duration; adjuvant group 21.7 months, no adjuvant group 17.6 month (p>0.05). This study strongly suggests that CMT can increase the median response duration and survival especially in patients with locally advanced head and neck squamous cell carcinoma who showed responses after the neoadjuvant chemotherapy with infusional 5-FU and cis-platin, but phase III randomized controlled prospective studies are warranted for the verification of this study.
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Two Cases of Spontaneous Pneumothorax During Chemotherapy
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Hyung Keun Roh, Nae Chun Yoo, Wha Young Lee, Hyun Cheol Chung, Jae Kyung Roh, Byung Soo Kim
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J Korean Cancer Assoc. 1989;21(2):448-454.
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Abstract
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- Spontaneous pneumothorax usually occurs abruptly without antecedent trauma to the chest. This diagnosis is subdivided into primary spontaneous pneumothorax, which accurs in healthy individuals without any known etiology, and secondary spontaneous pneumothorax, which is associated with underlying lung disease. There are many etiologic lung diseases producing secondary spontaneous pneumothorax, which is rare in lung cancer as a complication. Moreover, the occurrence of spantaneous pneumothorax after chemotherapy is very rare. The mechanism far development of spontaneous pneumothorax in primary or metastatic lung cancer has been described as a rupture of an emphysematous bulla in an overexpanded portion of lung partially obstructed by neoplasm, or an actual rupture of peripheral necrotic tumor into the pleural space. And effective chemotherapy may increase the risk of spontaneous pneumothorax in patients with manifest or occult lung metastases by inducing rapid lysis of the tumor tissue and by interfering with repair process. This report describes two cases of repeated spontaneous pneumothorax after chemotherapy in a patient with osteosarcoma and another patient with epithelioid sarcoma, and discusses possible pathophysiologic mechanisms.
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KCA
