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High frequency of hand foot syndrome with capecitabine

Kamil M, Haron M, Yosuff N, Khalid I, Azman N

J Coll Physicians Surg Pak, 2010 Jun;20(6):421-2.
PMID: 20642979 DOI: 06.2010/JCPSP.421422

A hospital based cross-sectional retrospective study was conducted to determine the frequency of hand foot syndrome (HFS) with Capecitabine as a single agent and in combination with Oxaliplatin. The study included 43 consecutive cases of colorectal carcinoma and conducted from June till December 2008. Patients on palliative care were excluded. SPSS was used for the application of chi-square test, by keeping the level of significance as p < 0.05. Fifteen (34.9%) patients developed HFS, 10 in the single-agent and 5 in the combination group. No significant association of HFS with either regimens was noted (p=0.876).

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Fulltext Hippuric acid nanocomposite enhances doxorubicin and oxaliplatin-induced cytotoxicity in MDA-MB231, MCF-7 and Caco2 cell lines

Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Bullo S

Drug Des Devel Ther, 2013;7:25-31.
PMID: 23345969 DOI: 10.2147/DDDT.S37070

The aim of the current study is to design a new nanocomposite for inducing cytotoxicity of doxorubicin and oxaliplatin toward MDA-MB231, MCF-7, and Caco2 cell lines. A hippuric acid (HA) zinc layered hydroxide (ZLH) nanocomposite was synthesized under an aqueous environment using HA and zinc oxide (ZnO) as the precursors.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Heterogeneity in cancer cells: variation in drug response in different primary and secondary colorectal cancer cell lines in vitro

Arul M, Roslani AC, Cheah SH

In Vitro Cell Dev Biol Anim, 2017 May;53(5):435-447.
PMID: 28120247 DOI: 10.1007/s11626-016-0126-x

Tumor heterogeneity may give rise to differential responses to chemotherapy drugs. Therefore, unraveling tumor heterogeneity has an implication for biomarker discovery and cancer therapeutics. To test this phenomenon, we investigated the differential responses of three secondary colorectal cancer cell lines of different origins (HCT116, HT29, and SW620 cells) and four novel primary cell lines obtained from different colorectal cancer patients to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) and explored the differences in gene expression among the primary cell lines in response to exposure to cytotoxic drugs. Cells were exposed to different doses of 5-FU and L-OHP separately or in combinations of equitoxic drug or equimolar drug ratios (median effect of Chou-Talalay principle). Cell viability was assessed using MTT assay and the respective IC50values were determined. Changes in gene expression in primary cell lines after exposure to the same drug doses were compared using real-time PCR array. The sensitivities (IC50) of different cell lines, both secondary and primary, to 5-FU and L-OHP were significantly different, whether in monotherapy or combined treatment. Primary cell lines needed higher doses to reach IC50. There were variations in gene expression among the primary cell lines of different chemosensitivities to the challenge of the same combined dose of 5-FU and L-OHP. The results confirm the heterogeneous nature of colorectal cancer cells from different patient tumors. Studies using primary cancer cells established from patient's tumors rather than secondary cell lines will more closely reflect the actual character of the disease.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Multidrug resistance protein 2 genetic polymorphism and colorectal cancer recurrence in patients receiving adjuvant FOLFOX-4 chemotherapy

Mirakhorli M, Rahman SA, Abdullah S, Vakili M, Rozafzon R, Khoshzaban A

Mol Med Rep, 2013 Feb;7(2):613-7.
PMID: 23232902 DOI: 10.3892/mmr.2012.1226

Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene, is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism. The correlation of G1249A ABCC2 polymorphism with the development of colorectal cancer (CRC) and poor prognosis was evaluated in patients who were treated with fluorouracil/-leucovorin (FL) plus oxaliplatin (FOLFOX-4). A total of 50 paraffin‑embedded tissue samples collected from CRC patients were analyzed to identify the polymorphism. Patients were in stage II/III and received postoperative FOLFOX-4 chemotherapy. As a control group, an equal number of unrelated healthy subjects were enrolled in the study. The polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and results were compared with clinicopathological markers, early relapse and survival rates. During the 12 months of follow-up, local and distant recurrences were observed in 15 (30%) patients. No significant difference in the distribution of wild-type and polymorphic genotypes was observed between the patient and control groups and between the patients who experienced recurrence within 1 year and those who did not (all P>0.05). In conclusion, the G1249A polymorphism is not associated with CRC risk and early recurrence. However, significant correlation was observed between G1249A polymorphism and the overall survival and disease-free survival of the patients.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Hypersensitivity reactions to oxaliplatin in two asian patients

Ng CV

Ann Pharmacother, 2005 Jun;39(6):1114-8.
PMID: 15886290

To report 2 cases of hypersensitivity reactions associated with oxaliplatin treatment in Asian patients.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Fulltext Prognostic factors and the role of adjuvant chemotherapy in post-curative surgery for Dukes B and C colon cancers and survival outcomes: a Malaysian experience

Hassan AS, Naicker M, Yusof KH, Wan Ishak WZ

Asian Pac J Cancer Prev, 2015;16(6):2237-43.
PMID: 25824744

BACKGROUND: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection. However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for disease characterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determine survival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia.

MATERIALS AND METHODS: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy for Duke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collected retrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meier survival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportional hazards regression with both univariate and multivariate analyses.

RESULTS: The survival analysis demonstrated a 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to 28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6% compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independent prognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008), serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007).

CONCLUSIONS: In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improves survival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be proven for Dukes B disease, our results suggest survival improvement in selected cases.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Fulltext Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study

Cheng AL, Cornelio G, Shen L, Price T, Yang TS, Chung IJ, et al.

Clin Colorectal Cancer, 2017 06;16(2):e73-e88.
PMID: 27780749 DOI: 10.1016/j.clcc.2016.08.005

BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed.
PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated.
RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations.
CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage
Adaptation of international guidelines for metastatic colorectal cancer: an asian consensus

Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.

Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Matched MeSH terms: Organoplatinum Compounds/administration & dosage