Carboplatin Combination Chemotherapy Research Articles

P2-232: Phase II study of weekly paclitaxel plus carboplatin combination chemotherapy in patients with advanced non-small cell lung cancer

P2-232: Phase II study of weekly paclitaxel plus carboplatin combination chemotherapy in patients with advanced non-small cell lung cancer

P2-266: A phase II study of the combination chemotherapy of Docetaxel and Carboplatin in advanced non–small cell lung cancer

P2-266: A phase II study of the combination chemotherapy of Docetaxel and Carboplatin in advanced non–small cell lung cancer

Serum amylase is a sensitive tumor marker for amylase-producing small cell lung cancer?

A 68-year-old male smoker was diagnosed as having amylase-producing small-cell lung cancer (SCLC). The serum amylase level was elevated, at 1756 IU/l, and the isozyme pattern was salivary type. Serum levels of "the tumor markers" CEA and NSE were 10.0 ng/ml and 22.6 ng/ml, respectively, but the level of pro-GRP was within the normal range. He was treated with combination chemotherapy of carboplatin and irinotecan. After completion of the chemotherapy, the serum amylase level decreased below the cutoff range and a computed tomography (CT) scan of the chest revealed marked reductions of the tumor in the primary site and in the lymph node metastasis. In November 2003, he was noted to have a slightly raised amylase level, of 168 IU/l, and raised levels of tumor markers. At this time, a CT scan, bone scintigraphy, and magnetic resonance imaging (MRI) of the brain demonstrated no recurrence. However, in December, MRI of the brain showed multiple metastases, and the recurrence of SCLC was thus confirmed. For the treatment of disease progression, the same regimen of chemotherapy as that given initially was administered. CT imaging revealed a partial response in the primary site and lymph node metastasis, and the serum amylase level decreased to 91 IU/l. After the completion of the second chemotherapy regimen, he underwent cranial irradiation and further chemotherapy. However, unfortunately, he died owing to deterioration of lung cancer. In this patient, the serum amylase level was found to be a highly sensitive marker of lung cancer.

Weekly combination chemotherapy of docetaxel and carboplatin and 5-FU in recurrent cervix cancer

16038 Background: The current phase II study assessed docetaxel/carboplatin/5FU given weekly for 24 weeks, for recurrent uterine cervix cancer. Methods: Fourty patients with histologically confirmed, recurrent uterine cervix cancer were enrolled. The patients eligible for this study had histologically confirmed, recurrent uterine cervix cancer. . Patients received weekly docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly with bolus 5FU 500 mg/m2. The response status of the patients was assessed using the common ECOG response criteria. Results: 40 patients were entered in this study. The distribution of intial stage at first presentation was IB, 6 ; IIB, 16; IIIB, 10; IVB, 8. There were 30 squamous cell carcinomas, 6 adenocarcinomas, 4 adenosquamous cell carcinoma. : All patients were evaluable, and completed all planned therapy. The most frequent maximum toxicities during chemotherapy were Grade 2 mucositis with neutopenia. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. Responses after 6 months included 6 patients with complete responses, 22 patients with PR and 12 patients with SD. No progression of disease was observed. Conclusions: This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. No significant financial relationships to disclose.

A combination phase I study of topotecan with carboplatin for relapsed small cell lung cancer: Results of West Japan Thoracic Oncology Group trial (WJTOG0202)

18126 Background: Topotecan is an active agent for relapsed or recurrent SCLC. Combination chemotherapy of topotecan and carboplatin for relapsed SCLC has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a phase I study was conducted. Method: Patients with measurable disease and one prior chemotherapy regimen excluding topotecan were enrolled in this study. Topotecan was administered through days 1 to 5, whereas carboplatin was administered on day 5. Courses were repeated every 3 weeks. The starting doses of topotecan and carboplatin were 0.50 mg/m2/day and AUC=5, respectively. The dose levels examined are shown in the table below. Results: A total of 32 patients with relapsed SCLC have been enrolled. Patient characteristics are as follows: median age, 64 yrs (range 43–74); male/female, 23/9; ECOG PS 0/1, 15/17 patients. Dose-limiting toxicities (DLTs) were observed in 1 patient at dose level 1 (infection), level 3 (diarrhea), and level 5 (thrombocytopenia), respectively. Three of 6 patients have experienced DLTs at dose level 6 (thrombocytopenia). MTD of topotecan and carboplatin were determined to be 0.85 mg/m2 and AUC=5, respectively. Five of 29 (17 %) assessable patients have responded to treatment with a partial response (PR), and 13 (45 %) patients have had stable disease (SD) at best response. Conclusions: The recommended doses are 0.75 mg/m2 of topotecan and AUC=5 of carboplatin. The combination of topotecan and carboplatin shows an acceptable activity and toxicity profile in relapsed SCLC patients. Further study in the phase III setting is warranted. [Table: see text] No significant financial relationships to disclose.

Segundas líneas en cáncer de ovario: ¿hay un estándar?

Recurrent ovarian carcinoma is usually incurable and palliative chemotherapy is the treatment of choice. In those patients considered as platinum-sensitive (with a platinum-free interval over 6 months) we have enough evidence to recommend carboplatin-based combination chemotherapy, due to the impact in survival observed in clinical trials comparing carboplatin monotherapy versus combination chemotherapy. On the other band, in those patient with progression to a platinum based chemotherapy (refractory) or with relapse in a period of less than 6 months (resistant), sequential monotherapy with active drugs in the second line is the recommended approach. The absence of a standard drug in this context makes that the choice should be based on toxicity criteria, quality of life and the preference of the patient.

Unsuccessful rechallenge with pemetrexed after a previous radiation recall dermatitis

Radiation recall dermatitis is characterized by an inflammatory reaction within a previously irradiated volume after administration of a drug. Antineoplastic drugs have mainly been involved in radiation recall reactions. This phenomenon is well known but poorly understood. Many hypotheses as stem-cell depletion in the radiotherapy field, heritable mutations within surviving stem cells, local vascular changes as well as a drug hypersensitivity reaction have been proposed to explain these reactions. In this report, we describe a non-small cell lung cancer patient treated with a carboplatin plus gemcitabine combination chemotherapy as first line followed by pemetrexed as second line therapy. Twenty-five years ago, she completed radiation therapy for breast cancer. Three days after the first cycle of pemetrexed, she presented with a radiation recall dermatitis. As EGFR-staining was negative, we rechallenged the patient with pemetrexed. Unfortunately, although less intense, we faced a recurrence of the skin reaction and pemetrexed was no longer continued.

A phase II trial of fractionated irinotecan plus carboplatin for previously untreated extensive-disease small cell lung cancer

Irinotecan plus cisplatin has been previously documented to be effective in the treatment of extensive-disease small cell lung cancer (ED-SCLC). This study was undertaken to investigate the efficacy and feasibility of combination chemotherapy of irinotecan and carboplatin in previously untreated ED-SCLC. From December 2002 to October 2005, 39 patients with previously untreated ED-SCLC were enrolled. Patients were treated with irinotecan (50mg/m(2) IV on days 1, 8, and 15) and carboplatin (target AUC=5 IV on day 1) every 4 weeks for up to six cycles. Thirty-four patients (87.2%) were male and the median age was 65 years. ECOG performance status was 0-1 in 20 (51.3%) patients and 2 in 19 (48.7%) patients. The median number of chemotherapy cycles was six (range: 1-6 cycles). Thirty-five patients were assessable for response evaluation. The overall response rate was 69.2% (1 CR, 26 PR) under the intent-to-treat analysis. After a median follow-up of 22.7 months, the median time to progression was 6.4 months (95% confidence interval [CI]: 5.7-7.1 months) and median overall survival was 11.0 months (95% CI: 9.9-12.0 months). The estimated 1-year survival rate was 42.5%. In terms of toxicities, Grade 3/4 neutropenia and thrombocytopenia occurred in eight (25.6%) and five (15.4%) patients, respectively. Grade 3/4 non-hematologic toxicities included diarrhea (10.3%), anorexia (7.7%), infection (10.3%), and neutropenic fever (12.8%). There was one treatment-related death due to superimposed infection on the broncho-pleural fistula. The combination chemotherapy of irinotecan and carboplatin was effective and tolerable in previously untreated ED-SCLC patients.

A combination chemotherapy of carboplatin and irinotecan with granulocyte colony-stimulating factor (G-CSF) support in elderly patients with small cell lung cancer

We have previously reported that carboplatin plus etoposide is an effective and relatively non-toxic regimen in elderly patients with small cell lung cancer (SCLC). Recently, the Japan Clinical Oncology Group reported that irinotecan plus cisplatin was more effective than etoposide plus cisplatin in the treatment of non-elderly patients with extensive disease (ED)-SCLC. Therefore, we conducted a prospective feasibility study designed specifically to evaluate the efficacy of carboplatin (day 1) and irinotecan (days 1, 8, 15) with granulocyte colony-stimulating factor (G-CSF) support in elderly SCLC patients. Three carboplatin AUC and irinotecan dose levels were used: 4 mg/ml x min and 50 mg/m2, respectively (level 1); 5 mg/ml x min and 50 mg/m2, respectively (level 2), and 5 mg/ml x min and 60 mg/m2, respectively (level 3). Although a phase I trial using this drug combination against non-SCLC performed at our institution found that the recommended dose was level 3, as the current trial included only elderly patients, the starting dose used was level 2. However, if a patient had history of prior chemotherapy, performance status (PS) of 2, or was aged 75 years or more, the dose administered was reduced by 1 level. If a patient had a PS of 0, the dose was increased by 1 level. Cycles were repeated every 4 weeks, and patients aged 70 years or more with a PS of 0-2 were eligible. Eighteen patients were enrolled, of which nine were given the level 1 dose, seven the level 2 dose, and two the level 3 dose. The patient group had a median age of 75 years, 8 patients had limited disease (LD) versus 10 with ED, 9 had received previous treatment for SCLC versus 9 previously untreated, and 13 had a PS of 0-1 versus 5 with a PS of 2. Seventeen (94%) patients received two or more cycles of chemotherapy, and the median actual delivery of irinotecan was 84% of the projected dose. Grade 3/4 neutropenia, anemia, and diarrhea occurred in 50%, 33% and 6% of patients, respectively. Other toxicities were mild and no treatment-related deaths occurred. The response rate was 89%, with two complete responses and 14 partial responses. The median survival time was 13.3 months and the 1-year survival rate was 62%. The combination of carboplatin and irinotecan with G-CSF support was an effective and non-toxic regimen in elderly SCLC patients and should be further evaluated in phase III trials.

Neurologic Improvement after High-dose Intravenous Immunoglobulin Therapy in Patients with Paraneoplastic Cerebellar Degeneration Associated with Anti-Purkinje Cell Antibody

Paraneoplastic cerebellar degeneration (PCD) is a rare syndrome associated with systemic malignancies, most in lung and ovarian cancer. Cerebellar ataxia has previously been associated with the presence of anti-Purkinje cell antibodies (anti-Yo) in the serum and cerebrospinal fluid and responses to therapy are uncommon. We reported two patients were identified with delayed onset of PCD associated with high titer of CSF anti-Yo (1:30,000, 1:320 U/ml) and a marked elevation of tumor markers for ovarian cancer (CA-125 17,700 ng/ml, 43 ng/ml) titer 1 year and 6 months prior to discovery of the carcinoma. Both developed subacute onset of severe ataxia, dysarthria, tremor, nystagmus with progression to severe debilitation (wheelchair bound or bedridden status). One of these patients also developed dysphagia that required PEG tube feeding. They were treated with six cycles of intravenous immunoglobulin (IVIG) 0.4 gm/kg/day x 5 days, every 4-6 weeks in conjunction with combination chemotherapy of Taxol and Carboplatin after the surgical resection of ovarian cancer. In each case, a significant improvement of neurological deficits were seen after the third cycle of IVIG, approximately 4 months after initiation of treatment. This type of delayed response is contrary to the previous reports. Both patients could ambulate without assistance in correlation with dramatic decrease in anti-Yo titer (1:80, 1:320 U/ml) and CA-125 (11 ng/ml, 8 ng/ml). This is a first report of benefit from IVIG in patients with late onset of PCD, which showed a delayed response with significant neurological improvement.

A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer

We conducted this phase II study to explore the efficacy and safety of weekly paclitaxel combined with carboplatin in elderly patients with advanced non-small cell lung cancer (NSCLC). Elderly patients (> or = 70 years old) of stage IIIB, IV, or recurrent NSCLC with PS 0 or 1 were enrolled. Patients received paclitaxel at a dose of 70 mg/m2 on Days 1, 8, 15, and carboplatin at the target dose of the area under the curve (AUC) of six on Day 1 every 28 days for at least two cycles. Forty-two patients were enrolled and 40 patients were treated with a median of three cycles (range, 1-5). The overall response rate (ORR) was 45% (95% confidence interval, 30-60%). The median survival time (MST) was 14 months and the 1-year survival rate was 62%. Twenty-eight patients (70%) had grade 3/4 neutropenia and two patients (5%) experienced grade 3 febrile neutropenia. Non-hematological toxicities were generally mild to moderate and grade 3 peripheral neuropathy was seen in one patient (3%). There was one treatment-related death by infection due to neutropenia. Weekly paclitaxel and carboplatin combination chemotherapy was an effective and safe regimen in elderly patients with advanced NSCLC. A randomized trial comparing this treatment with the conventional tri-weekly regimen of paclitaxel and carboplatin is warranted.

Prognostic significance of p53 mutation in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin

The prognostic significance of p53 mutation, microsattelite instability and DNA mismatch protein hMLH1 expression in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin was evaluated. The overall combination chemotherapy response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than those with wild-type p53 tumors (35/42 (83%) vs. 32/58 (55%); P=0.003 and 18/42 (43%) vs. 16/58 (28%); P=0.03, respectively). This tendency apparently existed in non-serous carcinoma, but not in serous carcinoma. Univariate analysis showed that the risk of death due to disease and risk of progression was significantly lower among patients with p53 mutation ( P=0.0357 and 0.0281, respectively). However, the presence of microsattelite instability or loss of hMLH1 expression was not associated with either the clinical response or prognosis. Determining p53 mutational status can be useful in predicting therapeutic response to drugs in ovarian carcinoma, especially in non-serous tumors.

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Objective: To investigate the inhibitory effects of combination chemotherapy of Carboplatin (CBP), Teniposide (Vm-26), Methasquin (MTX), and Nimodipine (NIM) on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods: MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sensitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP+NIM, Vm-26+NIM, MTX+NIM, CBP+Vm-26+MTX, or CBP+Vm-26+MTX+NIM, respectively. Results: The inhibition rate of CBP+Vm-26+MTX+NIM combination administration against glioma cells was 96.64%, higher than that of CBP+NIM (69.03%), Vm-26+NIM (71.53%), MTX+NIM (52.75%), CBP+Vm-26+MTX (78.59%) (P<0.01), and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion: The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.

Complete response to docetaxel and carboplatin combination chemotherapy for a stage IV uterine papillary serous carcinoma: a case report

We report a case of a stage IV uterine papillary serous carcinoma (UPSC) with multiple organ metastases. The patient was treated with docetaxel and carboplatin combination chemotherapy. After five courses, uterine tumor, Douglas tumor, lymphadenopathy, and distant metastases on magnetic resonance imaging or computed tomography scan were completely resoluted. Moreover, endometrial biopsy showed no carcinoma tissues after six courses. We suggest that this regimen may be effective for treatment of advanced-stage UPSC.

Complete response to docetaxel and carboplatin combination chemotherapy for a stage IV uterine papillary serous carcinoma: a case report

Complete response to docetaxel and carboplatin combination chemotherapy for a stage IV uterine papillary serous carcinoma: a case report

P-569 Efficacy and survival benefit of prophylactic Shakuyaku-Kanzou-Tofor myalgia/arthralgia following carboplatin and paclitaxel combination chemotherapy for non-small cell lung cancer

P-569 Efficacy and survival benefit of prophylactic Shakuyaku-Kanzou-Tofor myalgia/arthralgia following carboplatin and paclitaxel combination chemotherapy for non-small cell lung cancer

A preliminary report of irinotecan and carboplatin combination chemotherapy in extensive-disease small-cell lung cancer

7283 Purpose: The combination chemotherapy of irinotecan and cisplatin has been previously reported to be effective in the treatment of extensive-disease small-cell lung cancer (ED-SCLC). We conducted a phase II trial of the combination chemotherapy of irinotecan and carboplatin in replace of cisplatin in untreated ED-SCLC to evaluate the efficacy and toxicities. Methods: From Jan. 2003 to Aug. 2004, 24 patients (pts) with previously untreated ED-SCLC were enrolled. Pts were treated with irinotecan (50mg/m2 i.v. on day 1, 8 and 15) and carboplatin (target AUC=5 i.v. on day 1) every 4 weeks for up to 6 cycles. Results: The pts characteristics were as follows: median age 63 yrs (range, 39–72 yrs), ECOG PS 0–1/2 13/9, male/female 22/2. Median 5 cycles of chemotherapy (range, 1–6 cycles) and total 105 cycles was given to pts. Twenty one pts were assessable for response and toxicity. The median follow-up duration was 8months (range, 4–23 months). By intent-to-treat analysis the overall response rate was 75% (1 CR, 17 PR and 3 PD). The median time to progression was 6 months (95% CI: 4–7months). The median response duration and overall survival time was not reached. Major toxicityis was myelosuppression. G3/G4 neutropenia and thrombocytopenia occurred in 12.4% and 6%, respectively. G3/4 non-hematoloic toxicities included diarrhea (3%), infection (2%) and nausea (3%). There was one treatment-related death because of superimposed infection on bronchopleural fistula. Conclusion: The combination chemotherapy of irinotecan and carboplatin was effective and tolerable in ED-SCLC. No significant financial relationships to disclose.

Triplet combination of gemcitabine, paclitaxel, and carboplatin followed by maintenance 5-fluorouracil and leucovorin in patients with metastatic nasopharyngeal carcinoma

5572 Background In the treatmen of metastatic nasopharyngeal carcinoma (NPC), standard 2-drug chemotherapy gives a response rate of 60–70%, with median survival of about 12 months. We explore the possibility of improving treatment results by using a 3-drug combination, followed by maintenance treatment. Methods Patients with World Health Organization (WHO) type II or III metastatic NPC, who have not received chemotherapy for the metastatic disease, are eligible. They must be aged 18–70, have good performance status, and have adequate bone marrow, hepatic and renal functions. Treatment consists of a 3-drug combination chemotherapy of paclitaxel (70mg/m2), carboplatin (area under curve of 2.5) and gemcitabine (1000mg/m2), given on days 1 & 8 every 21days, up to a maximum of 6 cycles. Patients who have achieved partial or complete response will continue to receive weekly 5-fluorouracil (450mg/m2) and leucovorin (30mg/m2) up to a maximum of 48weeks. The primary endpoint is to assess response rate of the 3-drug combination, and secondary endpoints to evaluate toxicities and durability of response. The planned sample size is 28 patients. Results The study was started in September 2003. Twenty-four patients have been enrolled, of which 19 are males and 5 are females. The median age is 47, range 31–63. Eighteen patients are evaluable for response. One patient achieved a complete response, 15 had partial responses, giving an overall response rate of 89%. The main toxicity is marrow suppression, with 78% of patients experiencing at least one episode of grade 3 or 4 neutropenia, 28% had grade 3 or 4 thrombocytopenia, and 33% had grade 3 anemia. Conclusions This regimen is effective for metastatic NPC. It remains to be seen if this regimen with its maintenance component improves durability of response and survival. No significant financial relationships to disclose.

Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials: Bokemeyer C, Kollmannsberger C, Stenning S, Hartmann JT, Horwich A, Clemm C, Gerl A, Meisner C, Rückerl CP, Schmoll HJ, Kanz L, Oliver T, Department of Hematology/Oncology, University of Tuebingen, Tuebingen, Germany.

To study the role of single agent carboplatin chemotherapy in patients with metastatic seminoma based on the data from two randomised trials. In subgroup analyses in patients with different disease characteristics, the outcome treated with either single agent carboplatin or cisplatin-based combination chemotherapy was compared. Individual patient data from two randomised European trials involving patients with metastatic seminoma were gathered. The primary endpoint for all analyses was progression-free survival. The source data of 361 patients, 184 treated with cisplatin-based combinations and 177 treated with carboplatin single agent therapy, were entered into the analysis. Patient characteristics were comparable among the cisplatin-based and the carboplatin single agent treated patient groups with lymph nodes and lungs being the most frequent metastatic sites in 92 and 8% of patients, respectively. Overall, patients treated with single agent carboplatin had an inferior 5-year overall (89 and 94%; P = 0.09) and progression-free survival rate (72 and 92%; P < 0.0001) compared with patients receiving cisplatin-based combinations. For all investigated subgroups (based on age, prior radiation therapy, metastatic sites), carboplatin single agent therapy was found to be inferior to cisplatin-based combination chemotherapy. In conclusion, carboplatin single agent therapy cannot be recommended as standard treatment for any patient subgroup with advanced metastatic seminoma and cisplatin-based combination regimens remain the standard of care.

Neutropenic Enterocolitis in Lung Cancer: A Report of Two Cases and a Review of the Literature

The first patient, a 68-year-old woman, presented neutropenic fever and hemorrhagic diarrhea on the sixth day of a combination chemotherapy of carboplatin and paclitaxel. The second patient, a 30-year-old man, presented neutropenia and diarrhea on the tenth day of the second cycle of a combination chemotherapy of cisplatin and vinorelbine. In both patients, abdominal computed tomography scan showed thickening of the colon wall and pericolic edema, and the ultrasonography revealed echogenic thickening of the colon walls. These findings confirmed the diagnosis of neutropenic enterocolitis. After the treatments, we changed the anticancer drug regimen; and successfully achieved partial responses.