Toxicity In Small Cell Lung Cancer Research Articles

Specific sensitivity of small cell lung cancer cell lines to the snake venom toxin taipoxin

Small cell lung cancer (SCLC) is a malignant disease, for which no satisfactory treatment is presently available and consequently, new specific therapeutic targets are in high demand. A global gene expression analysis previously performed, identified the neuronal pentraxin receptor (NPR) as highly and relatively specifically expressed in SCLC, consistent with the neuroendocrine features of this cancer. Normally, NPR is exclusively expressed in neurons, where it associates with the homologous proteins neuronal pentraxins 1 and 2 (NP1 and NP2) in complexes capable of binding the snake venom neurotoxin taipoxin. The purpose of the present study was to assess the toxic effect of taipoxin in SCLC-cell lines and to determine if toxicity correlates to NPR and NP1 and NP2 expression levels. NPR was detected by Western blot analysis in all the tested SCLC and in control cell lines of different origin. The receptor co-purified with cell membrane in SCLC, indicating that NPR is surface associated. Microarray signals for NP1 and NP2mRNA was detected in a subset of SCLC-cell lines and validated by Northern blot analysis. Furthermore, NP1 protein was detected by Western blot analysis in a few SCLC-cell lines, but not in the control cell lines. A number of SCLC-cell lines showed marked sensitivity to taipoxin (IC50: 3-130 nM) at toxin concentrations leaving the control cell lines unaffected. The sensitivity to taipoxin did not correlate with the expression levels of NP1 protein and NP2-mRNA, suggesting that expression of these proteins may not be required for taipoxin induced toxicity in SCLC. The demonstrated toxic effect of taipoxin in SCLC may prove to be of importance for designing novel specific treatment modalities for this disease.

Influence of Sex on Toxicity and Treatment Outcome in Small-Cell Lung Cancer

Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC. This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival. Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v 69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001). Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival.

Influence of gender on treatment outcome and toxicity in small cell lung cancer (SCLC)

7041 Background: Female gender has been shown consistently to be a favourable prognostic factor in SCLC. Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of gender related toxicity in SCLC. Methods: This was a gender-based retrospective analysis of 4 SCLC trials, which were conducted by the NCIC CTG between 1981 and 1996. All 1006 patients (648 male, 358 female) received similar chemotherapy consisting of cyclophosphamide/ doxorubicin/vincristine and etoposide/ cisplatin . Toxicities examined included myelosuppression, stomatitis, vomiting and infection. Other endpoints included number of dose reductions required, number of omitted cycles, response rates and overall survival. Toxicities between the genders were compared using chi-square test in univariate analyses and logistic regression adjusting for age, BSA, performance status, LDH and individual trial in multivariate analyses. Results: Women experienced significantly more toxicity in both univariate and multivariate analyses (see Table). However, toxic death rates were similar for men and women (1.5% vs 1.1%, p=0.58). Despite increased toxicity, 76% of females vs 73.4% of males received all 6 treatment cycles (p=0.38), but 52% of females vs 43.4% of males had treatment delayed for ≥ 2 weeks (p=0.022). The ORR was 80.3% for females and 66.9% for males (p<0.0001) and the median survival was 1.31 years for females and 0.91 for males (p<0.0001) Conclusions: Women clearly experience more chemotherapy related toxicity in the treatment of SCLC, but this does not result in more toxic deaths or omitted treatment cycles, nor does it compromise outcome. No significant financial relationships to disclose.

Influence of gender on treatment outcome and toxicity in small cell lung cancer (SCLC)

7041 Background: Female gender has been shown consistently to be a favourable prognostic factor in SCLC. Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of gender related toxicity in SCLC. Methods: This was a gender-based retrospective analysis of 4 SCLC trials, which were conducted by the NCIC CTG between 1981 and 1996. All 1006 patients (648 male, 358 female) received similar chemotherapy consisting of cyclophosphamide/ doxorubicin/vincristine and etoposide/ cisplatin . Toxicities examined included myelosuppression, stomatitis, vomiting and infection. Other endpoints included number of dose reductions required, number of omitted cycles, response rates and overall survival. Toxicities between the genders were compared using chi-square test in univariate analyses and logistic regression adjusting for age, BSA, performance status, LDH and individual trial in multivariate analyses. Results: Women experienced significantly more toxicity in both univariate and multivariate analyses (see Table). However, toxic death rates were similar for men and women (1.5% vs 1.1%, p=0.58). Despite increased toxicity, 76% of females vs 73.4% of males received all 6 treatment cycles (p=0.38), but 52% of females vs 43.4% of males had treatment delayed for ≥ 2 weeks (p=0.022). The ORR was 80.3% for females and 66.9% for males (p<0.0001) and the median survival was 1.31 years for females and 0.91 for males (p<0.0001) Conclusions: Women clearly experience more chemotherapy related toxicity in the treatment of SCLC, but this does not result in more toxic deaths or omitted treatment cycles, nor does it compromise outcome. No significant financial relationships to disclose.