Chemotherapy In Treatment Of Women Research Articles

Reply to V. Pitini et al

We appreciate the comments of Pitini et al regarding our recent report of 7-year follow-up of cardiac function in National Surgical Adjuvant Breast and Bowel Project protocol B-31, which is evaluating the benefits and risks of adding trastuzumab to standard chemotherapy for the adjuvant treatment of women with early stage human epidermal growth factor receptor 2–positive breast cancer. We agree that a dynamic evaluation of cardiac function, for example by echocardiogram, provides more detailed assessment of myocardial function than multigated acquisition (MUGA) scans, and clearly all imaging modalities carry a margin of error. It is worth pointing out that for the first 1,000 patients enrolled onto B-31, the primary end point of the protocol was not the clinical efficacy of trastuzumab but cardiac safety. As such, patients with any significant cardiac condition were excluded from participation, including those with any arrhythmia requiring medication. The cardiac risk score applies only to those patients who would have met the eligibility requirements of the protocol from which it was developed. As we mentioned in the Methods section, MUGA scans were chosen over echocardiograms in order to write rules for holding or stopping trastuzumab and to minimize observer variability across institutions. We also agree that the accuracy of the baseline left ventricular ejection fraction (LVEF) measurement is critical, not only for the cardiac risk score, but also because it serves as the comparison point for subsequent LVEF measurements in determining whether to hold or continue trastuzumab. For instance, if a patient is dehydrated when her baseline LVEF study is performed, the value obtained may be higher than a true reflection of her level of systolic function, and the difference between baseline and subsequent measurements then may be exaggerated, in some cases potentially affecting decisions about whether to hold or continue trastuzumab. Finally, we welcome the important work that is being done using biomarkers such as ultrasensitive troponin, and we cite two such studies in our discussion. In the end, however, any indicators of potential cardiac risk, whether by risk score, biomarkers, or genetics, must be integrated into clinical decision algorithms regarding optimal use of trastuzumab in the treatment of patients with breast cancer.

Consistency of In Vitro Chemoresponse Assay Results and Population Clinical Response Rates Among Women With Endometrial Carcinoma

There are a number of equally efficacious chemotherapy options for the treatment of women with endometrial cancer, all of which work in only a subset of those women with this disease. An in vitro assay performed before therapy initiation to identify the drug(s) most likely to be effective for the individual patient would have clinical utility. Such an assay should yield response rates similar to those found in treated patient populations. The purpose of this investigation was to determine whether the patterns of in vitro tumor response rates as determined by ChemoFx are consistent with expected population response rates. Nine hundred twenty-three tumor specimens from patients with high-risk early-stage, advanced stage, or recurrent endometrial cancer were sent for testing with the ChemoFx drug response marker from August 2, 2006, to August 31, 2009. Tumors were categorized as responsive (R), intermediately responsive (IR), or nonresponsive to each drug or combination tested. Response rates from clinical trials were identified and compared with the corresponding in vitro response rates. Of the 923 specimens received, 759 (82%) were successfully tested by ChemoFx. Of these, 755 were tested for at least 1 of 5 National Comprehensive Cancer Network-recommended endometrial cancer drugs. The response rates (R+IR) for these drugs were as follows: 66% carboplatin-paclitaxel, 48% carboplatin, 37% cisplatin, 23% doxorubicin, and 36% paclitaxel. Moreover, 20% of tumors were pan-sensitive (R or IR) to all 5 regimens tested, 27% were pan-resistant (nonresponsive), and 53% showed different degrees of response to different drugs. ChemoFx in vitro response rates were consistent with published population response rates, and the ChemoFx drug response marker may provide clinically useful information to better optimize individual chemotherapy for treatment of women with endometrial cancer.

Intraperitoneal chemotherapy in the first‐line treatment of women with stage III epithelial ovarian cancer

Because women with advanced ovarian cancer have poor outcomes, it is imperative to continue exploring for novel therapies. The opportunity for intraperitoneal treatment, especially in the subgroup of patients with minimal residual disease, in which the intraperitoneal approach may have a biologic rationale for benefit over and above the standard intravenous route, needs to be explored to the fullest extent. The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2006 for randomized trials that compared first-line intraperitoneal-containing chemotherapy with first-line intravenous chemotherapy in the treatment of women with stage III epithelial ovarian cancer. Seven randomized, controlled trials were identified, including 3 large Phase III trials and 4 smaller randomized trials. The 3 large Phase III trials detected statistically significant overall survival benefits with intraperitoneal cisplatin-containing chemotherapy compared with intravenous chemotherapy alone. The improvements in survival were 8 months, 11 months, and 16 months, respectively. Pooled analysis from 6 of the 7 randomized trials confirmed the survival effect with intraperitoneal chemotherapy compared with intravenous chemotherapy alone (relative risk, 0.88; 95% confidence interval, 0.81-0.95). Severe adverse events and catheter-related complications with intraperitoneal chemotherapy were significantly more common and often were dose-limiting. The results from this review indicated that cisplatin-containing intraperitoneal chemotherapy should be offered to patients on the basis of significant improvements in overall survival. The appropriate clinical and institutional multidisciplinary facilities are needed for the safe delivery of this treatment in optimally debulked patients. Further research is needed concerning specific aspects of the treatment, such as optimal agent, dose, and scheduling.

Attitudes and practices regarding adjuvant chemotherapy in node-negative breast cancer

Eight months after an NCI "Clinical Alert" was issued a survey was conducted to examine attitudes and practices regarding the use of adjuvant chemotherapy for node-negative breast cancer among Connecticut physicians most experienced in the care of such patients. Respondents (N = 66) indicated that the communication prompted change in case management practices; 65% reported increased use of adjuvant chemotherapy in treatment of women with node-negative disease. Seventy-seven percent of physicians who responded now consider adjuvant chemotherapy for node-negative patients to be the standard of care in their community. Opinions regarding the NCI strategy were more equivocal, with 44% of respondents terming the issuance of the Clinical Alert "inappropriate." Our findings suggest that real change in the treatment of breast cancer may have been precipitated by the NCI's action.