Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer

OBJECTIVE: The purpose of this study was to determine the activity and toxicity of carboplatin and paclitaxel (taxol) in the treatment of advanced or recurrent endometrial cancer. STUDY DESIGN: This was a retrospective review of 18 consecutive patients with advanced (stage 4) or recurrent endometrial adenocarcinoma that had been treated with outpatient carboplatin and taxol. Taxol was delivered at 135 mg/m 2 over 3 hours, and carboplatin was delivery at an area under the curve of 5 over 1 hour. Cycles were repeated every 21 days. RESULTS: The overall response rate was 63% with 28% of patients who had a partial response and 35% of patients who had a complete response. Kaplan-Meier test was used to estimate the median survival time of 27 months and the median progression free survival time of 24 months. No patient had neutropenia, thrombocytopenia or grade 3 vomiting, neurosensory toxicity, or renal toxicity. CONCLUSION: Carboplatin and taxol for the treatment of advanced or recurrent endometrial cancer appear to be active regimens with minimal toxicity.     

Iniparib plus paclitaxel and carboplatin as initial treatment of advanced or recurrent uterine carcinosarcoma: a Gynecologic Oncology Group Study

Objective

To estimate the activity and tolerability of iniparib plus paclitaxel and carboplatin as initial therapy of uterine carcinosarcoma.

Methods

Eligible patients had advanced, persistent or recurrent carcinosarcoma of the uterus, measurable disease and no prior chemotherapy. Patients received paclitaxel 175 mg/m² IV over 3 h followed by carboplatin area under the curve (AUC) = six over 30 min on day one of 21 day cycles plus iniparib 4 mg/kg IV over 1 h twice weekly beginning on day one. Treatment continued until disease progression or adverse effects prohibited further therapy. Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to grade adverse events. The primary endpoint was tumor response. The study was conducted with a 2-stage group sequential design, targeting 20 and 25 patients in each stage. The study was designed to distinguish between 45% versus 65% responding with alpha = 10% and 90% power.

Results

Twenty-two patients were entered onto the study with five excluded from analysis, leaving 17 evaluable for analysis. Treatment resulted in the expected hematologic and non-hematologic toxicities of the paclitaxel-carboplatin backbone. The observed proportion responding was 23.5% (4/17 patients). The two-sided, 90% confidence interval for the true probability of response was 8.5-46.1%. The required minimal number of responses to proceed to second stage was eight.

Conclusions

Iniparib plus paclitaxel and carboplatin did not show significant activity to warrant further study. The rate of exclusion upon central pathology review (23%) suggests that review of pathology slides for confirmation of eligibility is important in this tumor type.     

Clinical experience with combination paclitaxel and carboplatin therapy for advanced or recurrent carcinosarcoma of the uterus

OBJECTIVE: The purpose of the study was to evaluate the efficacy of combination chemotherapy with paclitaxel and carboplatin in patients with advanced or recurrent carcinosarcoma of the uterus. METHODS: A retrospective review was carried out at Miyagi Prefecture Cancer Research Center Hospital. Six patients pathologically diagnosed with uterine carcinosarcoma were treated with paclitaxel (175 mg/m(2) given intravenously over 3 h) and carboplatin (dosed at AUC 6) every 3 weeks at our center between 1997 and 2003. Responses and adverse effects were assessed according to Response Evaluation Criteria in Solid Tumors and National Cancer Institute-Common Toxic Criteria, respectively. RESULTS: All six patients were evaluable for toxicity, and no unacceptably severe toxicities were reported. Grades 3 and 4 hematologic toxicities occurred, but all of them were overcome by adequate treatment with granulocyte colony-stimulating factor and blood transfusions. Five of six patients had measurable disease and thus were evaluable for response: Four patients had a complete response (CR) and the remaining patient had progressive disease (PD). The median progression-free interval (PFI) for all six cases was 18 months, with a median overall survival of 25 months. CONCLUSIONS: Although the number of cases was small, the regimen evaluated in the current study demonstrated higher activity and lesser toxicity than those found in previous studies in patients with advanced or recurrent uterine carcinosarcoma. Additional phase II clinical studies are necessary to evaluate fully the benefits of this regimen.     

Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1-13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.     

Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m²), doxorubicin (50 mg/m²), and cyclophos-phamide (500 mg/m²) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1–13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.     

Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma

Purpose

Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC.

Methods

A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150?mg/m²), epirubicin (50?mg/m²) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175?mg/m²) and carboplatin (AUC 5).

Results

TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p?=?0.017 for progression-free survival and p?=?0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p?=?0.55 for progression-free survival and p?=?0.63 for overall survival).

Conclusions

TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.     

Treatment of advanced ovarian carcinoma with carboplatin and paclitaxel in a patient with renal failure

Abstract. Jeyabalan N, Hirte HW, Moens F. Treatment of advanced ovarian carcinoma with carboplatin and paclitaxel in a patient with renal failure.
Platinum-based chemotherapy is the standard treatment for ovarian cancer. Since carboplatin elimination occurs largely through the kidneys, its use in patients with hemodialysis-dependent renal failure requires dose adjustments befitting the level of renal function. We employed the AUC (area under the concentration-time curve)- directed dosing strategy (the Calvert formula) to determine the carboplatin dose appropriate for an ovarian cancer patient with renal failure. Our approach is compared and defended against the empiric and thrombocyte nadir-directed dosing strategies. Since carboplatin clearance follows creatinine clearance, we also provide a review of methods and formulas used to determine creatinine clearance. An accurate method to determine creatinine clearance will enable others to use the AUC-directed dosing strategy to establish the carboplatin dose appropriate for patients with some residual renal function.     

A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers

PurposeSelinexor, a selective inhibitor of nuclear export, monotherapy causes nuclear accumulation of tumor-suppressor proteins and has anti-tumor activity in ovarian and endometrial cancers. The safety and tolerability of oral selinexor plus intravenous carboplatin and paclitaxel chemotherapy (selinexor + CP) was evaluated in this population.Patients and methodsThis phase I, 3 + 3 dose-escalation study assessed 4 selinexor + CP regimens. Patients in cohorts of 3, regardless of disease type, were administered 1 of 4 alternating regimens (selinexor at 30 mg/m² or 60 mg plus CP at AUC 5 and 175 mg/m² or 80 mg/m², respectively) for 6–10 cycles (1 cycle = 21 days), followed by selinexor maintenance. Enrolled patients with ovarian cancer had received 1 prior platinum-based therapy. Patients with endometrial cancer were chemotherapy-naive or had received 1 prior platinum-based therapy. Response was evaluated every 9 weeks.ResultsTwenty-three patients were treated (5 serous ovarian cancer; 18 endometrial cancer, including 6 carcinosarcomas). The most common treatment-related adverse events (TRAEs) were thrombocytopenia (100%), leukopenia (91%), and hyperglycemia (87%). The most common grade 3/4 TRAEs were leukopenia (70%), neutropenia (70%), lymphopenia (61%), anemia (57%), and alanine transaminase increase (43%). One treatment-related dose-limiting toxicity (grade 3 syncope) occurred. Twelve patients achieved a partial response and 1 achieved a complete response. Responses to all four regimens were observed in ovarian and endometrial cancers.ConclusionsCombination selinexor + CP was safe and tolerated in advanced ovarian and endometrial cancers.     

Teniposide or carboplatin in patients with recurrent or advanced cervical carcinoma: A randomized phase II trial

Thomsen TK, Pfeiffer P, Bertelsen K. Teniposide or carboplatin in patients with recurrent or advanced cervical carcinoma: A randomized phase II trial. Int J Gynecol Cancer 1998; 8 : 310–314.
The aim of the present study was to investigate response rates, time to progression, and survival with teniposide or carboplatin in patients with advanced or recurrent cervical cancer and to estimate the toxicity of each drug regimen.
Twenty-eight patients with recurrent or advanced cervical cancer entered the study. Two patients were ineligible (severe renal impairment, n = 1; performance status 3, n = 1) and were excluded from the analysis. The remaining 26 patients were randomized to either carboplatin (400 mg/m² on day 1, intravenously every four weeks) or teniposide (125 mg/m² on days 1, 2 and 3, intravenously every four weeks). Twelve patients were randomized to the carboplatin arm and 14 patients to the teniposide arm. They were all comparable with respect to age, performance status, histology, primary FIGO stage, and prior therapy.
Response was seen in four patients in each group (33% and 29%, respectively), all but one being partial. (One patient in the teniposide group had complete response). Time to progression and median survival were similar in the two groups (median time to progression 20/17 weeks and median survival 40/41 weeks, respectively.)
In general, toxicity was moderate. Leukopenia (WHO grade 3 or 4) was seen in one patient treated with teniposide, and thrombocytopenia (WHO grade 3 or 4) in one patient treated with carboplatin. Eleven patients (79%) in the teniposide group had alopecia requiring a wig. The study implies that both drugs have some activity in cervical cancer. Carboplatin has the advantage that it can be administered on an out-patient basis.     

An economic analysis of dose dense weekly paclitaxel plus carboplatin versus every-3-week paclitaxel plus carboplatin in the treatment of advanced ovarian cancer

Objective

Compared with every-3-week paclitaxel (q3T) plus carboplatin, dose-dense weekly paclitaxel (ddT) plus carboplatin improved the survival of ovarian cancer patients. We performed a cost analysis comparing these two regimens.

Methods

Using a Markov decision model, an acceptable incremental cost-effectiveness ratio (ICER) per progression-free life-year saved (PFLYS) was estimated. Cost of drugs, growth colony-stimulating factors, and transfusions were derived from Medicare reimbursement data. Survival and rates of complications were estimated based on the clinical trial.

Results

Using a body weight and surface area of an average woman age 63, the estimated cost per cycle of ddT was $107 vs. $80 for q3T. The costs per cycle of combination chemotherapy including treatment administration were $873 for ddT and $535 for q3T. With a median progression-free survival (PFS) of 28 months with ddT vs. 17.2 months with q3T, the ICER was $5809 per PFLYS for ddT compared with q3T arm. Using a maximum ICER of $100,000 per LYS as cost-effective threshold, the ddT regimen was cost-effective. The ICER was most sensitive to the hazard rate for difference in PFS between the two regimens. A 4-month difference in PFS resulted in a $1200 change of ICER per PFLYS. The ICER was also sensitive to overall survival difference, rate of hematological toxicity, and rate of discontinuation.

Conclusions

In this economic model, dose-dense weekly paclitaxel is a cost-effective treatment option for advanced ovarian cancer.     

Ifosfamide, paclitaxel, and carboplatin, a novel triplet regimen for advanced, recurrent, or persistent carcinoma of the cervix: a phase II trial

Objectives

(1) To determine the response rate of advanced, recurrent, or persistent carcinoma of the cervix to ifosfamide, paclitaxel, and carboplatin chemotherapy; (2) to determine the progression free interval and survival rate in patients treated with this regimen; (3) to describe the toxicities associated with this regimen; and (4) to evaluate the quality of life of patients while on treatment.

Methods

Eligible patients had histologically proven stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. Chemotherapy was given on day 1 of a 28-day cycle: mesna (600 mg/m²) prior to ifosfamide (2 g/m²), paclitaxel (175 mg/m²), carboplatin (AUC 5). Response rates were determined according to RECIST criteria. Toxicity was graded according the National Cancer Institute's common toxicity criteria. Quality of life measurements were obtained using the FACT-Cx.

Results

Twenty-eight patients participated in this study, with 21 evaluable for response rate. Overall, 7 patients (33%) had a demonstrated objective response (4 complete responses, 3 partial responses). Stable disease was documented in 3 patients. The overall median survival for all patients was 10 months. Median progression free survival for evaluable patients was 5.0 months. Bone marrow suppression was the most common toxicity. There were no negative effects of this treatment regimen on quality of life assessments.

Conclusion

Ifosfamide, paclitaxel, and carboplatin is an effective regimen in treating advanced or recurrent carcinoma of the cervix and has an acceptable toxicity profile.     

Activity of chemotherapy with carboplatin plus paclitaxel in a recurrent mesonephric adenocarcinoma of the uterine corpus

BACKGROUND: Malignant lesions derived from mesonephric (Wolffian) remnants are uncommon. The course of these tumors is usually indolent, and the recurrence has only been documented in nine cases. Because of the small number of cases, no current recommendations exist regarding treatment, and little is known about the response to chemotherapeutic agents. CASE: A 33-year-old woman was diagnosed with a mesonephric adenocarcinoma arising in the uterine corpus. Ten months after initial surgery and radiotherapy she presented with local and pulmonary relapse. Salvage chemotherapy with carboplatin plus paclitaxel was administered with a good response. CONCLUSIONS: Mesonephric adenocarcinomas are uncommon neoplasms. Their treatment remains elusive. We report a case of a recurrent uterine mesonephric adenocarcinoma that presented a good response to therapy with carboplatin plus paclitaxel. A review of the previous literature is also presented.     

Second-line with paclitaxel and carboplatin for recurrent disease following first paclitaxel and platinum compounds in ovarian carcinoma

OBJECTIVE: The combination of paclitaxel and platinum compounds is considered the best first-line regimen for advanced ovarian carcinoma. The purpose of this study was to evaluate a paclitaxel and carboplatin combination in pretreated patients who recurred within 24 months after a complete clinical response with the same regimen used as first-line chemotherapy. METHODS: 18 patients were included in this study. Second-line chemotherapy consisted of paclitaxel, 175 mg/m2 as a 3-hour infusion, and carboplatin AUC 6 every 21 days. RESULTS: Among 15 evaluable patients, eight (53%) complete and five (34%) partial responses were observed, while two (13%) patients had stable disease (SD). The response rate was 67% among patients with measurable disease and 52% for evaluable disease. The median progression-free interval after second-line chemotherapy was 8.3 months. The median progression-free interval for patients with measurable disease was 8.6 months and for evaluable disease it was 7.9 months. Seven (46%) of 15 patients have developed recurrence after second-line chemotherapy with paclitaxel and carboplatin with a median time to recurrence of 9.8 months. CONCLUSION: Paclitaxel 175 mg/m2 and carboplatin AUC 6 as second-line chemotherapy in this sensitive population is effective in terms of response rate and progression-free interval.     

A multi-institutional phase II trial of paclitaxel and carboplatin in the treatment of advanced or recurrent cervical cancer

Objective

The aim of this prospective trial was to evaluate the efficacy and safety of the combination of paclitaxel and carboplatin (TC) in patients with metastatic or recurrent cervical cancer.

Methods

This was a multicenter phase II trial of 3 weekly paclitaxel 175 mg/m² 3-hour iv day 1 followed by carboplatin AUC5 1-hour iv day 1 for maximum of 6 cycles until disease progression or prohibitive toxicity. Eligible patients had squamous or adenocarcinoma of the cervix with measurable stage IVB or recurrent, aged 20-75 years, Eastern Cooperative Oncology Group performance status 0-2, prior platinum-containing regimen 0-1, and no prior taxane. The primary endpoint was overall response rate (ORR) by RECIST.

Results

41 patients were enrolled, of which 39 were evaluable for analysis. 33 patients (84.6%) received prior radiotherapy. The confirmed ORR was 59% (95% CI, 43% to 75%); 5 patients (13%) achieved a complete response and median response duration was 5.2 months. The response rates for patients who had adenocarcinoma (n = 10) and prior platinum-based chemotherapy < 6 months (n = 7) were 40.0% and 0%, respectively. The median progression-free survival and overall survival times were 5.3 and 9.6 months, respectively. The most frequent grade 3 or 4 adverse events were neutropenia (79%), anemia (46%), thrombocytopenia (15%), and fatigue (8%). No treatment-related death was seen.

Conclusions

TC seemed to be feasible and effective similar to other cisplatin-based doublets for the treatment of metastatic or recurrent cervical cancer. Phase III trial is warranted to establish the clinical benefits of this combination.     

Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study

The aim of this study was to assess the efficacy and tolerability of paclitaxel and carboplatin (TC) in the treatment of patients with advanced or recurrent endometrial cancer. Patients eligible for this retrospective analysis had endometrial cancer with either advanced or recurrent measurable disease (untreated primary stage III/IV or stage III/IV patients with persistent, measurable disease [> or =2 cm] after surgery), Eastern Cooperative Oncology Group (ECOG) performance status > or =3, and received at least one cycle of TC. Response rates were determined using Response Evaluation Criteria in Solid Tumors criteria. Institutional Review Board approval was obtained prior to the initiation of this study. Eighty-five eligible patients, with a median age of 62 years (range 36-80) were identified. Fifty-seven (67%) of patients were treated at the time of recurrence. Prior radiation therapy had been used in the treatment of 36 (42%) patients, while 13 (15%) patients had received prior chemotherapy. Median follow-up time was 11.7 months (range 1.1-96.7 months), and the median number of cycles of therapy received was six (range 1-18). The overall response rate (ORR) was 43%, with a complete response rate of 5% and a partial response rate of 38%. Chemotherapy-naive patients had an ORR of 47%. Only seven (8%) patients had to discontinue therapy due to toxicity. Median progression-free survival was 5.3 months (95% CI, 4.6-7.4), with a median overall survival of 13.2 months (95% CI, 11.7-18.2). We conclude that TC is an active and tolerable regimen in the treatment of patients with advanced or recurrent endometrial cancer.