Clinical study on recombinant human interleukin-2 (Proleukin) in the treatment of metastatic renal cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of subcutaneous injection of recombinant human interleukin-2 (Proleukin) in the treatment of metastatic renal cell carcinoma (RCC).</p><p><b>METHODS</b>Forty-one patients with pathologically confirmed metastatic RCC after radical nephrectomy were enrolled into this study. Two or four consecutive cycles of subcutaneous injection of rhLL-2 were given, with each cycle duration of five weeks consisting of 4 weeks of treatment and one week of rest. The rhLL-2 was injected twice daily subcutaneously at a dose of 9 MIU on D1-D5 during week one, then 9 MIU twice daily on D1-D2 and followed by 9 MIU daily on D3-D5 during week 2-4. Patients were evaluated after the second cycle of treatment. If an objective response or stable disease was observed, the patient would receive another two cycles of treeatment.</p><p><b>RESULTS</b>Of the 41 patients, the overall objective response rate was 17.1% (95% confidence interval, 5.6% to 28.6%) with a complete response (CR) rate of 0.0% and partial response rate (PR) of 17.1%. However, nineteen patients (46.3%) still had a stable disease (SD), and 15 (36.6%) had progressed disease (PD). The disease control rate was 63.4% and the median time to progression (mTTP) was 6 months. The 1-year survival rate was 71.2% with a median overall survival (mOS) rate of 22.5 months. Among 36 PP population, the overall objective response rate was 19.4% (95% confidence interval, 6.5% to 32.3%) with CR rate of 0.0% and PR rate of 19.4%. Sixteen patients(44.4%) had stable disease, and 13 (36.1%) progressed disease. The disease control rate was 63.9%. The 1-year survival rate was 66.7% with a median time to progression of 6 months. The median overall survival (mOS) had not reached yet. The follow-up data showed that the long term survival of the patient who responsed to the IL-2 therapy can be prolonged. Severe toxicity (> or = grade III) was rarely observed. Grade I or II toxicities such as fatigue (100.0%) and fever (82.9%) were frequently observed but reversible.</p><p><b>CONCLUSION</b>Subcutaneous injection of recombinant human interleukin-2 may prolong the survival of patients with a metastatic renal cell carcinoma. This regimen is tolerable with rare severe toxicities.</p>

Gefitinib in the treatment of male patients with advanced non-small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the antitumor efficacy, time to tumor progression (TTP) and toxicity of gefitinib (Iressa, ZD1839)--a selective epidermal growth factor receptor tyrosine kinase inhibitor in the treatment of male patients with advanced non-small-cell lung cancer (NSCLC). Methods Fifty-nine male patients with stage IV NSCLC orally took Iressa 250 mg once daily until disease progression or intolerable toxicity ocurred. They were required to conduct tumor-evaluation before the treatment, one month after Iressa administration and then every other month.</p><p><b>RESULTS</b>Of these 59 patients, no complete regression was observed, 23.7% had partial response (PR), and 16.9% stable disease (SD) with a disease control (PR + SD) rate of 40.7%, while 59.3% had progress of disease (PD). The median time to tumor progression (TTP) was 1.8 months, and the median survival was 8.5 months. Fifty-nine patients were followed up over one year, 35 over two year and 15 over three year, and the 1-, 2- and 3-year survival rates were 42.4%, 17.1% and 13.3%. The most common adverse effects were grade 1 or 2 skin reaction and diarrhea.</p><p><b>CONCLUSION</b>Iressa is effective in antitumor for the male patients with advanced non-small-cell lung cancer, and can improve the survival for those responsing to gefitinib. The adverse effects are usually tolerable.</p>

A randomized trial of irinotecan plus fuorouracil and leucovorin with thalidomide versus without thalidomide in the treatment for advanced colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, side-effects and quality of life in the advanced colorectal cancer patients treated by irinotecan plus fuorouracil and leucovorin with thalidomide or without thalidomide.</p><p><b>METHODS</b>Eligible patients were randomly assigned to the treatment group and control group in a 1:1 ratio. In the treatment group, 32 evaluable patients were treated with irinotecan 180 mg/m2 i. v. on day 2, fuorouracil 400 mg/m2 bolus on day 1, 2 at a dose of 1200 mg/m2 civ. for 43 hours; leucovorin 200 mg/m2 i. v. on day 1, 2; thalidomide 300 mg, orally on day 1 - 14, two weeks as a cycle. In the control group, the regimen was the same as in the treatment group except oral intake of thalidomide.</p><p><b>RESULTS</b>The response rate was 28.1% in the treatment group vs. 15.2% in the control group (P = 0.2034) with a median TTP of 3.8 months vs. 2. 5 months (P = 0.1312). Furthermore, there was no statistically difference either between two groups regarding to adverse effects.</p><p><b>CONCLUSION</b>Irinotecan plus fuorouracil and leucovorin without oral intake of thalidomide is as effective and tolerable as irinotecan plus fuorouracil and leucovorin combined with oral thalidomide for advanced colorectal cancer.</p>

Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.</p><p><b>METHODS</b>In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.</p><p><b>RESULTS</b>In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.</p><p><b>CONCLUSION</b>Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.</p>

Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with cisplatin (DDP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Of 36 NSCLC patients consisting of 23 males and 13 females with a medium age of 52 years included, there were 26 adenocarcinomas, 7 squamous cell carcinomas, 1 adeno-squamous cell carcinoma and 2 unclassified types; 13 stage III B and 23 stage IV; 24 chemonaive and 12 previously treated by chemotherapy with a medium Karnofsky status of 90. All patients had measurable or evaluable parameters. The regimen was administered as following: CPT-11 60 mg/m2, IV, D1, 8 and 15; DDP 80 mg/m2, IV, D1; every 28 days as a cycle.</p><p><b>RESULTS</b>Totally, 97 cycles were carried out in these 36 patients with a medium cycles of 3. Of 35 evaluable patients, 22.9% (8/35) achieved partial response, 60.0% (21/35) had stable disease and 17.1% (6/35) progressive disease. The response rate was 29.2% (7/24) for chemonaive patients and 9.1% (1/11) for these previously treated. The 1-year survival rate was 45.4% with a medium time to tumor progression (TTP) of 199 days for the responders. The incidence rate of grade III/IV adverse events were: 16.7% for neutropenia, 13.9% alopecia, 5.6% diarrhea, 2.8% nausea and vomiting, respectively.</p><p><b>CONCLUSION</b>Irinotecan plus cisplatin is effective with tolerable adverse events in treating patients with advanced non-small cell lung cancer, but further investigation trials are needed.</p>

A randomized trial comparing oxaliplatin plus vinorelbine versus cisplatin plus vinorelbine for the treatment of patients with advanced non-small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the difference of efficacy, side-effects and quality of life in advanced non-small-cell lung cancer (NSCLC) patients treated with oxaliplatin plus vinorelbine or cisplatin plus vinorelbine.</p><p><b>METHODS</b>Eligible patients were randomly assigned to NL (oxaliplatin + vinorelbine) group and NP (cisplatin + vinorelbine) group in a 2:1 ratio. In the NL group, 70 evaluable cases were treated with oxaliplatin 130 mg/m(2) i.v. on day 2, and vinorelbine 25 mg/m(2) i.v. on days 1 and 8 in 21 days per cycle. In the NP group, 32 evaluable cases were treated with cisplatin 80 mg/m(2) i.v. divided to 2 - 3 days dosing, 21 days per cycle, and vinorelbine administered by the same way as in the NL group. The response rate, time to progression (TTP), one-year survival, side-effects and the quality of life were observed.</p><p><b>RESULTS</b>The response rate was 35.7% vs. 43.8% (P = 0.4), median TTP was 4.7 months vs. 5.5 months (P = 0.6), one-year survival rate was 38.5% vs. 58.6% (P = 0.07) in the NL and NP groups, respectively. Grade I-II neuro-sensory toxicity occurred significantly more frequent in NL group than in NP group (68.4% vs. 36.4%, P = 0.0017). However, Grade I-II granulocytopenia was significantly less occurred in NL group than in NP group (49.4% vs. 70.6%, P = 0.037). There was no statistically difference between the two groups regarding quality of life.</p><p><b>CONCLUSION</b>Due to good efficacy and tolerability, the NL regimen offered a new candidate for treating advanced NSCLC.</p>

Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Paclitaxel was used in a phase II trial in combination with cisplatin for esophageal cancer. The anti-tumor response, toxicity and survival of the treated patients were evaluated.</p><p><b>METHODS</b>Thirty patients with advanced, unresectable, or complicated with metastasis were allotted, twenty-seven patients had no prior chemotherapy while 3 patients had received adjuvant chemotherapy. Patients were given paclitaxel 175 mg/m(2) by 3-hour infusion on D1, and cisplatin 40 mg/m(2) daily on D2 and D3. Granulocyte colony-stimulating factor (G-CSF) was not routinely administered unless the patient had neutropenia. Treatment was recycled every 21 days.</p><p><b>RESULTS</b>Thirty patients (male/female, 28/2; median age 58) completed a median of 3 cycles and 27 patients were evaluable for response. Major objective responses were observed in 16 patients (59.3%; 95% confidence interval, 38.9% to 75.5%), including 5 complete responses (18.5%) and 11 partial responses (40.7%). The median time to tumor progression was 5.0 months (range, 1 to 23 months). The median actuarial survival was 9.7 months (range, 1 to 23 months). Twenty-eight patients were assessable for toxicity. The most common nonhematologic toxicity was alopecia. Grade 3 to 4 neutropenia was observed in 17.9% of the patients. Toxicity was manageable with dose attenuation and G-CSF support.</p><p><b>CONCLUSION</b>The combination of paclitaxel and cisplatin can be considered as a main regimen in the treatment of advanced esophageal cancer.</p>

IRESSA in the treatment of advanced non-small-cell lung cancer patients who failed to respond previous chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the antitumor efficacy, time to tumor progression (TTP) and toxicity of Iressa (ZD1839)-a selective epidermal growth factor receptor tyrosine kinase inhibitor in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond previous chemotherapy.</p><p><b>METHODS</b>Fifty-two patients with grade IV NSCLC previously treated with chemotherapy (77.0% of patients after second line therapy) received 250 mg of Iressa orally once daily until disease progression or development of intolerable toxic reaction. They were required to receive tumor-evaluation before the treatment, one month after Iressa administration and every other month thereafter.</p><p><b>RESULTS</b>Without complete regression being observed, partial response (PR) rate was 21.2% (11/52), stable disease (SD) 32.7% (17/52), disease control rate (PR + SD) 53.8%, progression of disease (PD) 46.2% (24/52); median time to tumor progression (TTP) was 3.5 month. Among them, 22 patients were followed up over one year and the 1-year survival rate was 31.8%. Symptomatic improvement rate was 52.9%. The most common adverse effects were skin reactions and diarrhea which were generally mild (grade 1 or 2). Only one patient withdrew from the trial because of grade III hepatic toxicity with increase in ALT and AST.</p><p><b>CONCLUSION</b>Iressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. It greatly alleviates tumor related symptoms. Adverse effects are generally tolerable. IRESSA is suitable for patients with poor performance status (ECOG > 2).</p>

Correlation between serum HER-2 oncoprotein and patients with breast cancer / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To detect serum HER-2 oncoprotein levels in patients with operable and metastatic breast cancers, and to study the correlations between serum HER-2 level and lymph node status as well as other clinical parameters.</p><p><b>METHODS</b>A total of 120 women were studied consisting of 10 healthy volunteers, 31 benign breast disease, 53 operable breast cancer, and 26 metastatic breast cancer patients. The levels of serum HER-2 were measured using an enzyme-liked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The mean serum HER-2 levels were 9.6 +/- 1.5 ng/mL in healthy volunteers, 11.9 +/- 1.6 ng/mL in benign breast disease, 13.2 +/- 4.2 ng/mL in operable breast cancer, and 30.5 +/- 30.8 ng/mL in metastatic breast cancer patients. The former is much lower than the latter three (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline, elevated serum HER-2 levels were observed in none of the healthy volunteers as well as patients with benign disease, but in 18.9% (10/53) operable breast cancer patients and 61.5% (16/26) metastatic patients. In patients with operable breast cancer, there was a positive correlation between serum concentrations of HER-2 and the size of primary tumor (P < 0.05), whereas there was no correlation between serum concentration and axillary lymph node or estrogen receptor status. In patients with metastatic disease, there was no correlation with site of metastases (P > 0.05).</p><p><b>CONCLUSION</b>Serum HER-2 level was strongly correlated with tumor loads and clinical stages, thus acting as a promising predictor of cancer recurrence in breast cancer patients.</p>

Recombinant human interleukin-11 in the prevention of chemotherapy-induced thrombocytopenia / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of domestic recombinant human interleukin-11 (rhIL-11) in the prevention of chemotherapy-induced thrombocytopenia.</p><p><b>METHODS</b>A randomized, self-crossover and placebo-controlled trial was conducted, with rhIL-11 and placebo classified randomly as drug A and drug B. Patients were randomly assigned to group AB or group BA. 25 microg/kg body weight of drug A or drug B was administered subcutaneously once daily starting 24 hours after chemotherapy and continued for 7 to 14 days or until the platelet count reached > or = 300 x 10(9)/L.</p><p><b>RESULTS</b>118 patients were evaluable in the efficacy study. When compared with the placebo treated cycle, the results showed that rhIL-11 was able to significantly increase the platelet count at the nadir and d21 after chemotherapy, with a increase of 60.7% and 86.1% (both P < 0.001). The mean duration of thrombocytopenia (< 100 x 10(9)/L) in rhIL-11 treated cycle was 1.0 +/- 2.0 days as compared to 6.9 +/- 5.3 days in placebo treated cycle. The side effects were ache (24.6%), swelling (16.1%) and knurl (11.9%) at the injection site, hyperaemia of conjunctiva (16.1%), edema (8.5%), palpitation (6.8%) and fatigue (5.1%).</p><p><b>CONCLUSION</b>rhIL-11, possessing significant thrompoietic activity, significantly increases the likelihood of avoiding chemotherapy-induced thrombocytopenia and shorten the duration of thrombocytopenia. Its side effects are mild and manageable.</p>

Recombinant Human Interleukin 11 (Mega) Promotes Thrombopoiesis in Cancer Patients with Chemotherapy-Induced Myelosuppression / 中国实验血液学杂志

A randomized, selfcross-over and placebo-controlled clinical trial has been taken to evaluated the curative efficacy of rhIL-11 (Mega) for thrombocytopenia in 29 cancer patients with severe myelosuppression induced by chemotherapy. Twenty-five micro g/kg of Mega or placebo was administered subcutaneously once daily starting 24 hours after the completion of chemotherapy, and continuing for 7 to 14 days or until the platelet count reached 300 x 10(9)/L. The results from those in 118 cases performed phase II clinical trial, showed that there were 29 cases with platelet count less than 50 x 10(9)/L in placebo cycle, but there was only 1 case in Mega cycle. The percentage of the patients with platelet count less than 50 x 10(9)/L in placebo cycle of placebo + Mega group was higher than that of Mega + placebo group. The nadir and platelet counts on day 21 after chemotherapy in Mega cycle were 2.04 and 1.43 times more than those in placebo cycle, respectively. The data show that Mega had significant thrombopoietic activity with a long lasting oction for the patients experienced severe myelosuppression. It significantly increases the likelyhood of avoiding thrombocytopenia in cancer patients undergoing chemotherapy and shortens the duration of thrombocytopenia.