paywalled- Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: A meta-analysis

Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: A meta-analysis

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Abstract

Background

Paclitaxel is commonly given as a 3-h infusion every 3 weeks for a variety of malignancies. Several randomized clinical trials comparing weekly paclitaxel with Q3-week (Q3W) have produced mixed results in terms of efficacy and toxicity creating controversy about the ideal dose and schedule.

Methods

A literature search using PubMed, Cochrane Library, and Proceedings of the American Society of Clinical oncology from 1995 to 2011 was performed..........Moderators of cancer types, ethnicity, and paclitaxel dose ratio were analyzed for primary dependent variables.

Results

Ten trials were included....

Conclusion

Weekly paclitaxel has a favorable toxicity profile compared to the current standard of Q3W paclitaxel.

paywalled- Gynecologic Oncology - Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer ($8,699,872 monthly.

ScienceDirect.com - Gynecologic Oncology - Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer

Objective

To determine the potential economic impact of a paclitaxel drug shortage in patients with newly diagnosed, untreated ovarian cancer.

Methods

A modified Markov state transition model with a 6 cycle time horizon compared two scenarios: (1) Standard treatment (STD): paclitaxel 175 mg/m2/carboplatin AUC 5 × 6 cycles; (2) Paclitaxel drug shortage (DS): docetaxel 75 mg/m2/carboplatin AUC 5 × 6 cycles. Adverse events, quality of life, and costs of chemotherapy, neuropathy, febrile neutropenia, and anemia were incorporated. Key assumptions: (1) Costs and consequences were assigned only to grade 2 + neuropathy, febrile neutropenia, and grade 3–4 anemia; (2) Grade 2 + neuropathy prompted a switch from paclitaxel/carboplatin to docetaxel/carboplatin or from docetaxel/carboplatin to carboplatin alone; (3) Febrile neutropenia resulted in inpatient hospitalization followed by G-CSF prophylaxis.

Results

The mean cost of 6 cycles of chemotherapy was $4939 in the STD and $16,107 in the DS scenario, for a cost difference of $11,168 per patient over 6 cycles of treatment. STD was the dominant strategy (less expensive and more effective than the drug shortage scenario). In sensitivity analysis, DS was more costly over a wide range of clinical estimates in each arm. A drug shortage that affects approximately 50% of women initiating chemotherapy is expected to impact 779 women and cost third party payers an additional $8,699,872 monthly.

Conclusions

Our model indicates that chemotherapy drug shortages can have a significant negative impact on the average cost of primary treatment for ovarian cancer and have the potential to negatively impact health system costs.

Current Drug Shortages: Paclitaxel Injection (updated)

Current Drug Shortages: Paclitaxel Injection (updated):

APP is currently back-ordered on 100 mg/16.7 mL vial (NDC 63323-0763-16) and 300 mg/50 mL vial (NDC 63323-0763-50). 30 mg/5 mL vial (NDC 63323-0763-05) is currently available.

Current Drug Shortages: Paclitaxel Injection (updated)

Current Drug Shortages: Paclitaxel Injection (updated):

Teva has all presentations available with ample inventory.

Carboplatin/Taxol/Ridaforolimus in Endometrial, Ovarian and Solids - Full Text View - ClinicalTrials.gov

Carboplatin/Taxol/Ridaforolimus in Endometrial, Ovarian and Solids - Full Text View - ClinicalTrials.gov

This study is currently recruiting participants.

Verified April 2012 by H. Lee Moffitt Cancer Center and Research Institute

First Received on December 1, 2010.   Last Updated on April 20, 2012   History of Changes

abstract: Effects on the immune system and toxicity of carboplatin/paclitaxel combination chemotherapy in patients with stage III-IV ovarian and non small cell lung cancer and its role in survival and toxicity.

 
Effects on the immune system and toxicity of carboplatin/paclitaxel combination chemotherapy in patients with stage III-IV ovarian and non small cell lung cancer and its role in survival and toxicity.


Abstract
 
Purpose:
To examine the impact of paclitaxel and carboplatin combination chemotherapy on the parameters of the immune system in patients with non small cell lung cancer (NSCLC) and with ovarian cancer before, during and after chemotherapy, and the effect of this combination on the overall patient survival.

Methods:
24 patients with NSCLC and 20 with ovarian cancer (all in stage IIIb-IV) treated with 6 courses of paclitaxel and carboplatin combination chemotherapy were separated into two groups according to their survival group A: long survival (> 12 months for NSCLC; > 30 months for ovarian cancer) group B: short survival (<12 months for NSCLC; <30 months for ovarian cancer).

At the same time we studied some immunological parameters (CD3, CD4, CD8, CD56, CD34, IL-3, IFN-γ) in relation with the induced toxicity during chemotherapy. The results were analysed using the ANOVA method.

Results: 
We observed a statistically significant difference of CD4 and CD4/CD8 after chemotherapy between groups A and B (p<0.001 and p< 0.006 respectively), implying that the further increase of T-helper cells after chemotherapy had a positive impact on survival. In addition, statistically interesting was the difference in values of IFN-γ between patients of groups A and B before and after chemotherapy (p< 0.039 and p< 0.027, respectively). Patients with high IL-3 had little chance of toxicity.

Conclusion:
Our findings support that with carboplatin/ paclitaxel combination chemotherapy, important parameters of the immune system (IFN-γ, CD4, CD4/CD8) can be used as prognostic factors for survival, while others (IL-3) as indicators of toxicity.

abstract: Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer (astounding figures)

Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer - NCBI

Abstract

OBJECTIVE:

To determine the potential economic impact of a paclitaxel drug shortage in patients with newly diagnosed, untreated ovarian cancer.

RESULTS:

...... A drug shortage that affects approximately 50% of women initiating chemotherapy is expected to impact 779 women and cost third party payers an additional $8,699,872 monthly.

CONCLUSIONS:

Our model indicates that chemotherapy drug shortages can have a significant negative impact on the average cost of primary treatment for ovarian cancer and have the potential to negatively impact health system costs.

abstract: Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy - Reeves - 2012 - Cancer - Wiley Online Library

Blogger's Opinion: since this journal is a publication of the ACS then open access should be mandated

Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy

Abstract

BACKGROUND:

Paclitaxel causes an acute pain syndrome (P-APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P-APS and eventual peripheral neuropathy symptoms.

METHODS:

Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy-Induced Peripheral Neuropathy 20-item instruments were completed weekly.

RESULTS:

The P-APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P-APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P-APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain.

CONCLUSIONS:

Patients with worse P-APS severities appear to have more eventual chemotherapy-induced peripheral neuropathy. This provides support for the concept that P-APS is a form of nerve pathology.

abstract: Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

Abstract

PURPOSE:

This phase I trial evaluated intraperitoneal (IP) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

Current Drug Shortages: Paclitaxel (Taxol) Injection (updated)

Current Drug Shortages: Paclitaxel Injection (updated):

Hospira product 30 mg/5 mL vial (NDC 0409-0342-09): ample levels of inventory to support market demand. Product 300 mg/50 mL vial (NDC 0409-0342-50): ample levels of inventory to support market demand. Product 100 mg/16.7 mL vial (NDC 0409-0342-22): next delivery April. Please check with your wholesaler for available inventory. Teva has 30 mg/ 5 ml vial on backorder until April 2012. All other presentations are available with ample inventory.

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study


Objective 
To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II–IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods 
Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60mg/m² on day 8. A standard 3+3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results 
Patients were treated with paclitaxel 175mg/m² IV and carboplatin IP from AUC 5–7 on day 1 and paclitaxel 60mg/m² IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), >2week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135mg/m² IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4cycles with one DLT (grade 3 hyponatremia).

Conclusions 
Paclitaxel at 175mg/m² IV, carboplatin AUC 6 IP day 1 and paclitaxel 60mg/m² IP day 8 yield 18–56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.

FDA U.S. Drug Shortages - Paclitaxel (Taxol)

Paclitaxel Injection (updated 3/2/2012)

Company/Products	Reason	Related Information
Sandoz: 1-800-525-8747 6 mg/mL injection 30 mg/5 mL vial (NDC 66578-0043-01) 100 mg/16.7 mL vial (NDC 66578-0043-02) 300 mg/50 mL vial (NDC 66578-0043-03)	Manufacturing delays	Sandoz is currently on backorder.
APP 1-888-386-1300 6 mg/mL injection 30 mg/5 mL vial (NDC 63323-0763-05) 100 mg/16.7 mL vial (NDC 63323-0763-16) 300 mg/50 mL vial (NDC 63323-0763-50)	Increase in demand	APP is on intermittent back order and is releasing product as it becomes available.
Hospira Inc. Customer Service: 1-877-946-7747 300 mg/50 mL vial (NDC 0409-0342-50) 30 mg/5 mL vial (NDC 0409-0342-09) 100 mg/16.7 mL vial (NDC 0409-0342-22)	Higher than anticipated market demand.	Product 30 mg/5 mL vial (NDC 0409-0342-09): ample levels of inventory to support market demand. Product 300 mg/50 mL vial (NDC 0409-0342-50): next delivery March. Product 100 mg/16.7 mL vial (NDC 0409-0342-22): next delivery April. Please check with your wholesaler for available inventory.
Bedford Laboratories 1-800-562-4797 6 mg/mL injection 30 mg/5 mL vial (NDC 55390-0114-05) 100 mg/16.7 mL vial (NDC 55390-0114-20) 300 mg/50 mL vial (NDC 55390-0114-50)	Manufacturing delays	Bedford has all paclitaxel presentations on backorder and the company cannot estimate a release date.
Teva 1-800-545-8800 6 mg/mL injection 30 mg/5 mL vial (NDC 00703-4764-01) 100 mg/16.7 mL vial (NDC 00703-4766-01) 150 mg/25 mL vial (NDC 00703-4767-01) 300 mg/50 mL vial (NDC 00703-4768-01)	Manufacturing delays	Teva continues to release Paclitaxel 30mg/5mL vial (NDC 00703-4764-01), Paclitaxel 100mg/16.7mL vial (NDC 00703-4766-01), Paclitaxel 150mg/25mL (NDC 00703-4767-01) and Paclitaxel 300mg/50mL (NDC 00703-4768-01) as it becomes available
Sagent Pharmaceticals 1-866-625-1618 30mg/5mL NDC 25021-213-05 100mg/16.7mL NDC 25021-213-17 300mg/50mL NDC 25021-213-50		Sagent has the 5mL and 16.7mL on allocation and the 50mL product is available.

abstract: Health-related quality of life in recurrent platinum-sensitive ovarian cancer—results from the CALYPSO trial

Background: In the CALYPSO trial, carboplatin–pegylated liposomal doxorubicin (CD) demonstrated superior therapeutic index versus carboplatin–paclitaxel (CP) in patients with recurrent ovarian cancer. This paper reports the health-related quality of life (HRQoL) findings.

Conclusions: These patient-reported outcomes confirm the overall lower toxicity of CD versus CP. The improved disease-related outcomes achieved with CD were not at the expense of QoL.

abstract: Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial (GINECO)

Conclusions: Combination chemotherapy in platinum-resistant ROC (recurrent ovarian cancer) was more toxic than weekly paclitaxel and did not significantly prolong PFS.

A Risk-Adapted Strategy of Adjuvant Paclitaxel/Carboplatin in Early-Stage Ovarian Cancer: Time-Dependent Effect of 4 versus 6 Cycles on Outcome.

Abstract

Objective:
We investigated the efficacy of risk-adapted adjuvant paclitaxel/carboplatin chemotherapy in early-stage ovarian carcinoma.

Methods: Fifty-three patients were treated according to the risk of relapse: patients with stages IA or IB or with grade 1 (low risk) received 4 cycles of paclitaxel and carboplatin; patients with IC/IIA and grade 2 or 3 (high risk) received 6 cycles of chemotherapy. The outcome was compared with that of 95 patients who were all treated with 4 cycles.

Results: Median follow-up was 88, 113 and 42 months for the whole cohort, non-risk-adapted and risk-adapted treatment, respectively.

Five-year relapse-free and disease-specific survival was 86 and 93% for the whole population, 96 and 97% for low-risk and 81 and 91% for high-risk patients.

Risk classification was the only significant prognostic factor for relapse-free (p = 0.011) and disease-specific survival (p = 0.039). Among high-risk patients, the administration of 6 cycles was associated with a significantly lower relapse rate after censoring events, which occurred beyond 2 years (3 vs. 18%; p = 0.013), but this difference was diminished at 5 years (23 vs. 25%; p = 0.797).

Conclusions: Six cycles of chemotherapy reduced the risk of relapse within 2 years, but the benefit from two additional cycles beyond this time is questionable.

Intravenous/Intraperitoneal Paclitaxel and Intraperitoneal C... : International Journal of Gynecological Cancer

Objective:
This study aimed to evaluate intravenous (IV)/intraperitoneal (IP) paclitaxel and IP carboplatin (TCipTip therapy) feasibility in epithelial ovarian (EOC), fallopian tube (FTC), or peritoneal carcinoma (PC) patients.


Methods:
From December 2007 to August 2010, 20 women with histologically confirmed stage IC to IV EOC, FTC, or PC.....

Phase II Study of Docetaxel Weekly in Combination With Carboplatin Every 3 Weeks as First-Line Chemotherapy in Stage IIB to Stage IV Epithelial Ovarian Cancer

 Objectives: 
The purpose of this study was to assess the response rate, toxicity, progression-free survival, and overall survival in a series of patients with advanced-stage ovarian carcinoma treated with a first-line weekly docetaxel and 3 weekly carboplatin regimen.
 
Conclusions:
The tolerable hematologic toxicity (no need for colony-stimulating factors) and the low rate of neurotoxicity (only grades 1–2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgery make this regimen an interesting alternative in selected patients.

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study

Highlights

► The maximum tolerated dose and feasibility of IV and IP chemotherapy was assessed.
► The dose limiting toxicity rate for Paclitaxel 175 mg/m² IV, carboplatin AUC 6 IP and paclitaxel IP was 35%.

Cochrane review: Short versus long duration infusions of paclitaxel for any advanced adenocarcinoma.

OBJECTIVES:

To assess the effectiveness and toxicity of short versus long infusions of paclitaxel for any advanced adenocarcinoma.

"Adverse events were not comprehensively reported for any of the other comparisons. Outcomes were incompletely documented and QoL outcomes were not reported in any of the trials. The strength of the evidence is weak in this review as it is based on meta analyses of very few trials or single trial analyses and all trials were at moderate risk of bias and two were published in abstract form only."

Abstract/full free access: Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/ refractory epithelial ovarian cancer