1.Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer.
Yang LIU ; Meng XIU ; Xiang WANG ; Qing LI ; Jia Yu WANG ; Ying FAN ; Qiao LI ; Shan Shan CHEN ; Rui Gang CAI ; Hong Nan MO ; Fei MA ; Yang LUO ; Bing He XU ; Pin ZHANG
Chinese Journal of Oncology 2022;44(2):178-184
Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Carboplatin/therapeutic use*
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Humans
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Neoadjuvant Therapy/adverse effects*
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Paclitaxel/therapeutic use*
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Treatment Outcome
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Triple Negative Breast Neoplasms/pathology*
2.Determination of carboplatin dose by area under the curve in combination chemotherapy for senile non-small cell lung cancer.
Tiejun, YIN ; Qingqing, LIU ; Changyao, HU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(6):710-2
To preliminarily determine the appropriate dosage of carboplatin (CBP) at AUC of 5 mg.Ml(-1).min(-1) in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer (NSCLC). Thirty-five Chinese senile patients with NSCLC in advanced stage (III/IV) were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol+CBP, Gemzar+CBP and NVB+CBP. The dose of CBP was at 5 mg.mL(-1).min(-1) of area under the concentration-time curve (AUC). Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% (46/96) of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% (27/96) of the subjects. However, other side effects were slight. The mean score of quality of life (QOL), according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL(-1).min(-1) by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL(-1).min(-1) by AUC may be too high for Chinese senile patients with non-small cell lung cancer.
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
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Area Under Curve
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Carboplatin/*administration & dosage
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Carboplatin/adverse effects
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Carcinoma, Non-Small-Cell Lung/*drug therapy
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Lung Neoplasms/*drug therapy
3.A Case of Pseudomenbranous Colitis after Paclitaxel and Carboplatin Chemotherapy.
The Korean Journal of Gastroenterology 2009;54(5):328-332
Antibiotics-associated pseudomembranous colitis is well documented and caused by abnormal overgrowth of toxin producing Clostridium difficile colonizing the large bowel of patients undergoing antibiotic therapy. Administration of chemotherapeutic agents is frequently complicated by diarrhea and enterocolitis. However, pseudomembranous colitis related to chemotherapeutic agent usage is very rare. We experienced a 67 old-years male patient diagnosed of non-small cell lung carcinoma who complained of watery diarrhea and abdominal pain after treated with paclitaxel and carboplatin. Sigmoidoscopic examination revealed diffusely scattered, whitish to yellowish pseudo-membrane with background edematous hyperemic mucosa from sigmoid colon to rectum. Histopathologic findings were consistent with pseudomembranous colitis as typical volcano-like exudate. The symptoms improved after stopping chemotherapy and treatment with metronidazole. In patients with persistent diarrhea and abdominal pain after receiving chemotherapy agents, although rare, pseudomembranous colitis should be considered as a differential diagnosis.
Aged
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Anti-Infective Agents/therapeutic use
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Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use
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Carboplatin/*adverse effects/therapeutic use
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Carcinoma, Non-Small-Cell Lung/drug therapy
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Diagnosis, Differential
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Enterocolitis, Pseudomembranous/*diagnosis/etiology/pathology
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Humans
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Lung Neoplasms/drug therapy
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Male
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Metronidazole/therapeutic use
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Paclitaxel/*adverse effects/therapeutic use
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Sigmoidoscopy
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Tomography, X-Ray Computed
4.Effectiveness and safety of recombinant human interleukin-11 in the treatment of chemotherapy-induced thrombocytopenia.
Wei LEI ; Jun LIANG ; Wei-Gang CHEN ; Xue-Zhen MA ; Mei XU ; Li-Li DU
Chinese Journal of Oncology 2006;28(7):542-544
OBJECTIVETo investigate the effectiveness and safety of domestically produced recombinant human interleukin 11 (rhIL-11) for the treatment of chemotherapy- induced thrombocytopenia.
METHODSA total of 32 solid cancer patients who developed chemotherapy-induced thrombocytopenia ( _70 x 10(9)/L) after the first cycle of chemotherapy was studied by self-cross control. The patients were given subcutaneous injection of rhIL-11 (25 microg x kg(-1) x d(-1)) for 7 to 14 consecutive days or until platelet count > or = 100 x 10(9)/L during the second cycle of chemotherapy using the identical regimen as in the first cycle.
RESULTSThe mean platelet count of the patients after rhIL-11 treatment was higher at different time points during the second cycle of chemotherapy than that during the first cycle of chemotherapy with the mean platelet count of (110.2 +/- 53.5) x 10(9)/L in the first cycle of chemotherapy versus (55.6 +/- 46.8) x 10(9)/L in the second cycle of chemotherapy (P < 0. 01). Patients with platelet count < or = 50 x 10(9)/L was 4/32 (12.5%) in the first cycle of chemotherapy and 12/32 (37.5%) in the second cycle of chemotherapy (P < 0.01). The time recovery to the normal platelet count was 2 - 18 days (median 5 days) in the first cycle of chemotherapy versus 5 - 27 days (median 12 days) in the second cycle of chemotherapy (P < 0.01). The case/frequency of the platelet transfusion was 2/2 in the first cycle of chemotherapy, while it was 7/9 in the second cycle of chemotherapy (P < 0.01). The major adverse reactions relative to rhIL-11 treatment were fatigue, myalgia/arthralgia, ache, headache, palpitation, edema and fever, most of which could be relieved automatically without any specific treament. However, some 3 grade side effects such as fatigue, myalgia/arthralgia and headache needed proper medication.
CONCLUSIONrhIL-11 is safe and effective for chemotherapy-induced thrombocytopenia with mild and manageable side effects.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; Fatigue ; chemically induced ; Female ; Humans ; Injections, Subcutaneous ; Interleukin-11 ; adverse effects ; genetics ; therapeutic use ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; Platelet Count ; Recombinant Proteins ; administration & dosage ; adverse effects ; therapeutic use ; Stomach Neoplasms ; drug therapy ; Thrombocytopenia ; chemically induced ; drug therapy ; Treatment Outcome
5.Induction concurrent chemoradiotherapy using Paclitaxel and Carboplatin combination followed by surgery in locoregionally advanced non-small cell lung cancer--Asian experience.
Swee-Peng YAP ; Wan-Teck LIM ; Kian-Fong FOO ; Siew-Wan HEE ; Swan-Swan LEONG ; Kam-Weng FONG ; Philip ENG ; Anne Al HSU ; Joseph Ts WEE ; Thirugnanam AGASTHIAN ; Heng-Nung KOONG ; Eng-Huat TAN
Annals of the Academy of Medicine, Singapore 2008;37(5):377-382
INTRODUCTIONIt has been established that combined chemoradiotherapy treatment benefits selected patients with stage III Non Small Cell Lung Cancer (NSCLC). However, locoregional recurrence still poses a problem. The addition of surgery as the third modality may provide a possible solution. We report our experience of using the triple-modality approach in this group of patients.
MATERIALS AND METHODSThis is a retrospective review of 33 patients with stage III NSCLC treated between 1997 and 2005. Patients have good performance status and no significant weight loss. There were 26 males (79 %) with median age of 63 years (range, 43 to 74) and median follow-up of 49 months. Seventy-six percent had Stage IIIA disease. Chemotherapy consisted of paclitaxel at 175 mg/m2 over 3 hours followed by carboplatin at AUC of 5 over 1 hour. Thoracic radiotherapy was given concurrently with the second and third cycles of chemotherapy. All patients received 50 Gray in 25 fractions over 5 weeks.
RESULTSThe main toxicities were grade 3/4 neutropenia (30%), grade 3 infection (15 %) and grade 3 oesophagitis (9%). Twenty-five patients (76%) underwent surgery. Of the 8 who did not undergo surgery, 1 was deemed medically unfit after induction chemoradiotherapy and 4 had progressive disease; 3 declined surgery. Nineteen patients (58 %) had lobectomy and 6 had pneumonectomy. The median overall survival was 29.9 months and 12 patients are still in remission.
CONCLUSIONThe use of the triplemodality approach is feasible, with an acceptable tolerability and resectability rate in this group of patients.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel ; adverse effects ; therapeutic use ; Pneumonectomy ; Radiotherapy, Adjuvant ; Retrospective Studies
6.A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC).
Bao-hui HAN ; Qing-yu XIU ; Hui-min WANG ; Jie SHEN ; Ai-qin GU ; Yi LUO ; Chun-xue BAI ; Shu-liang GUO ; Wen-chao LIU ; Zhi-xiang ZHUANG ; Yang ZHANG ; Yi-zhuo ZHAO ; Li-yan JIANG ; Chun-lei SHI ; Bo JIN ; Jian-ying ZHOU ; Xian-qiao JIN
Chinese Journal of Oncology 2011;33(11):854-859
OBJECTIVETo analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).
METHODSThis is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.
RESULTSThe objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05).
CONCLUSIONSCompared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.
Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Disease-Free Survival ; Double-Blind Method ; Endostatins ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Prospective Studies ; Quality of Life ; Remission Induction
7.Short-term intermittent prophylactic administration of recombinant human thrombopoietin attenuates chemotherapy-induced thrombocytopenia in lung cancer patients.
Yun-hua XU ; Bai-jun CHENG ; Shun LU ; Hong JIAN ; Zhen ZHOU ; Zhi-wei CHEN ; Xiang-yun YE
Chinese Journal of Oncology 2011;33(5):395-399
OBJECTIVETo evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients.
METHODS24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC).
RESULTSThe lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected.
CONCLUSIONProphylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.
Adenocarcinoma ; blood ; drug therapy ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Area Under Curve ; Carboplatin ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; blood ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use
8.Therapeutic effects and prognostic factors for the limited-stage small cell lung cancer treated with multidisciplinary therapy.
Xiao-jiao DONG ; Meng-zhao WANG ; Wei ZHONG ; Li ZHANG ; Xiao-tong ZHANG ; Jing ZHAO ; Ying XIA ; Long-yun LI
Chinese Journal of Oncology 2012;34(3):216-221
OBJECTIVETo study the differences of objective response rate (ORR), side effects and survival among patients with limited-stage small cell lung cancer (LD-SCLC), who received concurrent chemoradiotherapy, sequential chemoradiotherapy or chemotherapy alone, and to analyze the influencing factors on their survival.
METHODSOne hundred and sixty-six patients diagnosed as LD-SCLC in Peking Union Medical College Hospital from January 2000 to December 2009 were included in this study. The differences of objective response rates, side effects and survival rates were analyzed by χ2 test. Kaplan-Meier test was used to calculate the overall survival (OS) and progress-free survival (PFS). Cox regression was used to detect the influencing factors on survival time of the patients.
RESULTSThe patients were divided into three groups: concurrent chemoradiotherapy (49 cases), sequential chemoradiotherapy (62 cases) and chemotherapy alone (55 cases). The chemotherapy was based on CE/EP regimen, with an average cycle of 5.2. Radiotherapy was of a common or 3-dimensional conformal technology, for regular segmentation irradiation with an average dose of 49.6 Gy. The total ORR was 73.4%, OS and PFS were 22.9 months and 10.8 months, 1, 3, 5-year survival rates were 82.7%, 31.8%, 18.6%, respectively. For the concurrent group, sequential group and chemotherapy alone group, the ORR was 89.4%, 67.2% and 66.0%, respectively. Compared the chemotherapy alone group and concurrent group with the sequential group, there were significant differences (P<0.05). For the concurrent group, sequential group and chemotherapy alone group, the median OS was 29.7 months, 22.6 months, and 19.5 months; the median PFS was 12.7 months, 10.8 months, and 9.8 months, respectively, with a non-significant difference between each two groups (P>0.05). For the concurrent group, sequential group and chemotherapy alone group, the 1-year survival rates were 91.1%, 86.3%, and 65.6%, the 3-year survival rates were 44.2%, 28.3% and 22.8%, and the 5-year survival rates were 24.2%, 21.4% and 11.1%, respectively, with significant differences among them (P<0.05). The major side effects were myelosuppression, gastrointestinal reactions, radiation pneumonia and radiation esophagitis. For the concurrent group, sequential group and chemotherapy alone group, the incidence of myelosuppression were 84.4%, 76.8% and 60.0%, respectively, with a significant difference (P=0.008) between the concurrent group and chemotherapy alone group. For the concurrent group and sequential group, the incidences of radiation pneumonia were 22.2% and 22.9%, with a non-significant difference (P=0.940). The incidences of radiation esophagitis were 47.2% and 16.7%, respectively, with a significant difference (P=0.002). Multivariate analysis showed that OS was significantly associated with gender (P=0.018) and ECOG score (P=0.009), and PFS was significantly associated with gender (P=0.050).
CONCLUSIONSFor LD-SCLC, concurrent chemoradiotherapy can significantly increase the objective response rate. Concurrent chemoradiotherapy and sequential chemoradiotherapy compared with chemotherapy alone can extend survival, and concurrent chemoradiotherapy is better, but the differences among the three regimens are not significant. Gender and ECOG score are important influencing factors of survival.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; therapeutic use ; Chemoradiotherapy ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Epirubicin ; therapeutic use ; Esophagitis ; etiology ; Etoposide ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Middle Aged ; Myelopoiesis ; radiation effects ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; adverse effects ; Remission Induction ; Small Cell Lung Carcinoma ; drug therapy ; pathology ; radiotherapy ; Survival Rate
9.A randomized controlled trial of two chemotherapy regimens (paclitaxel liposome combined with platinum and paclitaxel combined with platinum) in concurrent chemoradiotherapy for cervical carcinoma.
Si-yuan ZENG ; Ling LI ; Mei-ling ZHONG ; Wei JIANG ; Yun-yan WU ; Yi LIU
Chinese Journal of Oncology 2011;33(7):517-519
OBJECTIVETo compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on the survival rate in patients with cervical carcinoma receiving concurrent chemoradiotherapy.
METHODSOne hundred and sixty two cases with primary cervical carcinoma diagnosed and treated in the Jiangxi Maternal and Children Hospital between January 2008 and November 2009 were enrolled in this randomized controlled trial. Seventy one cases were included in the paclitaxel group and 91 in the paclitaxel liposome group. The chemotherapy doses were as followings: paclitaxel liposome and paclitaxel 135 mg/m(2); cisplatin 80 mg/m(2) or carboplatin AUC 4 - 6, repeated every 21 days for two or three times. Radical radiotherapy was given to both groups at the same time. The efficacy was evaluated by the tumor regression and the patients were followed-up for six months.
RESULTSThe overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89.0%, respectively (P > 0.05). The 1-year cumulative survival rate was 91.4% for the paclitaxel group and 89.2% for the paclitaxel liposom group (P > 0.05). The incidence rate of adverse effects such as rash, gastrointestinal toxicity, bone marrow suppression and muscle/joint pain in the paclitaxel liposome group was significantly lower than that in the paclitaxel group (P < 0.05), while there was no significant difference regarding the hair loss, liver damage, and peripheral neuritis (P > 0.05).
CONCLUSIONSPaclitaxel liposome plus platinum is a safe and effective therapeutic regimen for stage IIa-IV cervical carcinoma. However, the long-term efficacy of this regimen should be further observed.
Adenocarcinoma ; pathology ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brachytherapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Squamous Cell ; pathology ; therapy ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; adverse effects ; Cobalt Radioisotopes ; therapeutic use ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Gastrointestinal Diseases ; chemically induced ; Humans ; Iridium Radioisotopes ; therapeutic use ; Liposomes ; administration & dosage ; adverse effects ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction ; Survival Rate ; Uterine Cervical Neoplasms ; pathology ; therapy
10.Efficacy of once-per-cycle administration pegylated recombinant human granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in a phase I trial.
Sheng YANG ; Yuan-Kai SHI ; Peng LIU ; Xiao-Hong HAN ; Xiao-Hui HE ; Yong-Ming CAI ; Zheng-Min CHEN
Acta Academiae Medicinae Sinicae 2006;28(3):339-344
OBJECTIVETo explore the efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prophylaxis of chemotherapy-induced neutropenia.
METHODSPatients with previously untreated non-small cell lung cancer or breast cancer and with normal bone marrow function were eligible for the trial. In the phase I trial, patients were to treated with two cycles of paclitaxel/carboplatin chemotherapy every 21 days. In cycle 1, if absolute neutrophil count (ANC) dropped below 1.0 x 10(9)/ L with fever and/or ANC dropped below 0.5 x 10(9)/L, rhG-CSF 150 microg/d was administrated until WBC > or = 10 x 10(9)/L or ANC > or = 5.0 x 10(9)/L. In cycle 2, patients were to receive a single injection of PEG-rhG-CSF (30, 60, 100, or 200 microg/kg) 48 hours after chemotherapy. Pharmacodynamic analyses were performed.
RESULTSAll the 16 patients enrolled (4 in each group) were eligible for efficacy evaluation. In cycle 1, 7 patients received rhG-CSF administration because of grade 4 neutropenia, while in cycle 2, there was only 1 episode of grade 4 neutropenia, which were in the 30 microg/kg group. In cycle 1, the mean ANC nadir of 1.37 x 10(9)/L occurred on day 13 in the 9 patients who received no rhG-CSF administration. In cycle 2, the mean ANC nadirs were 0.77 x 10(9)/L, 4.54 x 10(9)/L, 3.00 x 10(9)/L, and 5.56 x 10(9)/L, respectively, in 30, 60, 100, or 200 microg/kg group. The nadirs of the first two groups occurred on day 8 of cycle 2, while those of the other two groups appeared on day 7. After PEG-rhG-CSF administration, two mean ANC peaks were observed. The first one ranging from 20.87 x 10(9)/L to 33.61 x 10(9)/L in the 4 groups appeared on day 3 to day 4. In the 30 microg/ kg group, the mean ANC reached the second peak at 5.03 x 10(9)/L on day 14. The second peaks on day 10 in the other groups were 12.42 x 10(9)/L, 11.59 x 10(9)/L, and 18.92 x 10(9)/L, respectively. Pharmacodynamic analyses showed sustained serum concentrations of PEG-rhG-CSF during the period of neutropenia.
CONCLUSIONSPEG-rhG-CSF administration may decrease the incidence of grade 4 neutopenia and result in earlier and higher nadir ANCs. PEG-rhG-CSF has a potential of once-per-cycle administration. The ANC and serum concentration of PEG-rhG-CSF are consistent with neutrophil receptor-mediated clearance.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Female ; Granulocyte Colony-Stimulating Factor ; biosynthesis ; pharmacology ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Neutropenia ; chemically induced ; prevention & control ; Paclitaxel ; administration & dosage ; adverse effects ; Recombinant Proteins