Chemotherapy and skin reactions

Background

New chemotherapic agents and new protocols in oncology have led to an increasing survival rate in patients affected by tumors. However, this increased use has been accompanied by a growth in the incidence of cutaneous side effects and a worsening of patients’ quality of life. Appropriate management of skin toxicity associated with chemotherapic agents is therefore necessary for suitable drug administration and to improve quality of life and clinical outcomes.

Methods

We have clinically examined 100 patients affected by cancer, determining type, frequency, treatment, and evolution of side effects related to chemotherapy.

Results

The prevalent cutaneous side effects in patients undergoing chemotherapy are skin rash, xerosis, pruritus, paronychia, hair abnormality, and mucositis. The clinical cases are reported in detail.

Conclusion

Oncological therapies have become more selective and have low systemic toxicity because of their high specificity, but cutaneous side effects are common and may worsen the quality of life of these patients.     

Early Skin Toxicity as a Predictive Factor for Tumor Control in Hepatocellular Carcinoma Patients Treated with Sorafenib

Introduction.

Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients.

Materials and Methods.

All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand–foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response plus stable disease) and TTP.

Results.

Sixty-five HCC patients treated with sorafenib were included in this analysis: 47 (73.3%) received sorafenib after failure of some local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty-nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In patients who developed skin toxicity, the tumor control rate was 48.3%, versus 19.4% in patients without cutaneous side effects. The median TTP was 8.1 months in the group of patients with skin toxicity versus 4.0 months in those without skin toxicity. This difference was also statistically significant on multivariate analysis. A borderline statistically significant difference was also observed in terms of OS in patients with early skin toxicity.

Conclusions.

Skin toxicity should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy.     

Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant chemotherapy in esophageal cancer: phase II study

Purpose

Concomitant use of chemotherapy and a radiation dose schedule that is more efficient compared to conventional radiotherapy may provide better outcomes in patients with esophageal cancer. This study aimed to assess the efficacy and tolerability of neoadjuvant cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy regimen in this group of patients.

Methods and materials

A total of 20 newly diagnosed treatment-naïve esophageal cancer patients were included in the study. Neoadjuvant cisplatin and 5-FU were given with 28-day intervals in a total of three courses. Along with the third course of chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 day.

Results

All patients could receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade III acute toxicity (50%). None of the acute toxicity reactions required treatment discontinuation. Grade III or higher subacute/late toxicity occurred in 10 patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable disease, with only 1 patient (5%) having progressive disease. Seven patients underwent surgery. Overall, 8 patients (40%) had local control. The 5 years overall survival rate was 38.1%.

Conclusions

Neoadjuvant hyperfractionated accelerated radiotherapy plus chemotherapy may help to target local disease control and increase survival in patients with esophageal cancer. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum tumor control rates with minimal toxicity.Key Words: Neoadjuvant radiochemotherapy, esophageal cancer, hyperfractionated-accelerated radiotherapy, toxicity, safety     

Seasonal variation in the month of birth in patients with skin cancer

Background:

Month of birth influences the risk of developing several diseases. We investigated the influence of date of birth on melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC) incidence.

Methods:

Enhanced cancer registry data were analysed including 1751 MSC and 15 200 NMSC.

Results:

People born in February to April showed significantly elevated risks of NMSC compared with those born in summertime.

Conclusions:

We demonstrated seasonality by date of birth for skin cancer incidence. Neonatal UV exposure may explain this finding.     

An Ethnographic Study of Barriers to Cancer Pain Management and Opioid Availability in India

Background.

The world’s global cancer burden disproportionally affects lower income countries, where 80% of patients present with late-stage disease and have limited access to palliative care and effective pain-relieving medications, such as morphine. Consequently, millions die each year with unrelieved pain.

Objective.

The objective of this study was to examine barriers to opioid availability and cancer pain management in India, with an emphasis on the experiences of nurses, who are often the front-line providers of palliative care.

Methods.

Fifty-nine participants were recruited using a purposive, snowball sampling strategy. Ethnographic data collection included in-depth, semistructured interviews (n = 54), 400+ hours of participant observation, and review of documents over 9 months at a government cancer hospital in South India. Systematic qualitative analysis led to identification of key barriers that are exemplified by representative quotes.

Results.

Morphine is more available at this study site than in most of India, but access is limited to patients seen by the palliative care service, and significant gaps in supply still occur. Systems to measure and improve pain outcomes are largely absent. Key barriers related to pain management include the role of nursing, opioid misperceptions, bureaucratic hurdles, and sociocultural/infrastructure challenges.

Implications.

Interventions must streamline process details of morphine procurement, work within the existing sociocultural infrastructure to ensure opioids reach patients most in need, target unexpected audiences for symptom management education, and account for role expectations of health care providers.

Conclusion.

Macro- and micro-level policy and practice changes are needed to improve opioid availability and cancer pain management in India.     

Losses of chromosome 5q and 14q are associated with favorable clinical outcome of patients with gastric cancer

Purpose.

To improve the clinical outcome of patients with gastric cancer, intensified combination strategies are currently in clinical development, including combinations of more extensive surgery, (neo)adjuvant chemotherapy, and radiotherapy. The present study used DNA copy number profiling to identify subgroups of patients with different clinical outcomes. We hypothesize that, by identification of subgroups, individual treatment strategies can be selected to improve clinical outcome and to reduce unnecessary treatment toxicity for patients with gastric cancer.

Experimental Design.

DNA from 206 gastric cancer patients was isolated and analyzed by genomewide array comparative genomic hybridization. DNA copy number profiles were correlated with lymph node status and patient survival. In addition, heat shock protein 90 (HSP90) expression was analyzed and correlated with survival in 230 gastric cancer patients.

Results.

Frequent (>20%) DNA copy number gains and losses were observed on several chromosomal regions. Losses on 5q11.2-q31.3 and 14q32.11-q32.33 (14% of patients) were correlated with good clinical outcome in univariate and multivariate analyses, with a median disease-free survival interval of 9.2 years. In addition, loss of expression of HSP90, located on chromosome 14q32.2, was correlated with better patient survival.

Conclusion.

Genomewide DNA copy number profiling allowed the identification of a subgroup of gastric cancer patients, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 or low HSP90 protein expression, with an excellent clinical outcome after surgery alone. We hypothesize that this subgroup of patients most likely will not benefit from (neo)adjuvant systemic treatment and/or radiotherapy, whereas anti-HSP90 therapy may have clinical potential in patients with HSP90-expressing gastric cancer, pending validation in an independent dataset.     

Fat and epidermal cell suspension grafting: a new advanced one-step skin regeneration surgical technique

Background

Dystrophic skin scarring commonly occurs following skin cancer resections. In particular, the cosmetic outcome of skin graft reconstructions, following epidermoidal carcinoma removal, is generally poor due to wide marginal tumour excision, loss of subcutaneous tissues, and subsequent pigmented atrophic scarring of the graft coverage. Skin grafting sequelae need a three dimensional correction to restore either the epidermal layer or the dermal/subdermal volume and vascularization.

Methods

The surgeons combined CO₂ laser ablation, subdermal lipofilling according to the Coleman’s technique and epidermal cell suspension autografting to correct wide depressed and dyschromic facial scar. The Authors applied this new technique on three nasal skin cancer resected patients: two of them actually need a longer follow-up, the third patient, a 48 yr old caucasian male, presented a skin grafting scar due to sclerodermiform basal cell carcinoma removal. This case is reported discussing pre-intra and post-operative records up to a complete twelve months follow-up.

Results

Records at six and twelve months follow-up after surgery demonstrate a fully integrated skin graft and a good restoration of the treated area, presenting the same texture and pigmentation of the adjacent untreated skin. Optimal, stable three-dimensional skin cosmetic restoration was obtained in a single stage surgical procedure.

Conclusion

Autologous non-cultured epidermal cell suspension transplantation on an epidermal laser ablated skin area, in combination with lipofilling subdermal reconstruction, appears to be an effective, simple and time-saving method to correct skin graft sequelae, in skin cancer patients. This new technique allows to restore a three-dimensional morphological structure of the treated area and to recover a natural appearance of the skin at the same time. The Authors believe that this technique can be safely used to treat any kind of dystrophic scarring.     

Statin use is not associated with reduced risk of skin cancer: a meta-analysis

Background:

There is contradictory evidence about the association between statin and skin cancer.

Methods:

Literature search in PubMed and Web of Science was undertaken up to June 2013. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated.

Result:

A total of 21 articles with 29 studies were identified. No association was found between statin and skin cancer among neither melanoma (RR, 0.94; 95% CI, 0.85–1.04) nor non-melanoma skin cancer (RR, 1.03; 95% CI, 0.90–1.19).

Conclusion:

Our meta-analysis does not support a potential role of statin use in the prevention of skin cancer.     

Second malignancies in patients with primary central nervous system lymphoma

Background

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma with distinctive biological behaviors. The evolving treatment of PCNSL has greatly improved the outcome for patients with this disease and has stimulated interest in second malignancies (SMs) in patients diagnosed with PCNSL.

Methods

The records of 129 cases of PCNSL at Mayo Clinic, diagnosed between January 1, 1988, and November 26, 2012, were reviewed. Data on clinical characteristics, laboratory parameters, treatments, outcomes, and SMs were collected. The mean follow-up time was 44.8 months (range, 0.5–240 months; median, 28.0 months).

Results

Altogether, 28 cases with 30 (23.26%) SMs were identified. Twenty (15.50%) patients had prior or synchronous SM. Ten (7.76%) patients developed a subsequent primary cancer after PCNSL. The most common sites of prior or synchronous SMs were prostate (4/20), skin (4/20), and gastrointestinal (3/20). The most common site of the subsequent SM was skin (4/10). Two cases were identified with both prior SM and subsequent SM.

Conclusions

Second malignancies in cases with PCNSL were not uncommon and occurred in nearly a quarter of our cohort. Nonmelanoma skin cancers were frequently seen. Therefore, screening for SMs should also be considered in long-term follow-up of patients with PCNSL. In addition, the high incidence of subsequent cancer, synchronous cancer, and frequently seen nonmelanoma skin cancers may all indicate an immunosuppressed state in patients with PCNSL.     

Assessment of treatment-induced female sexual morbidity in oncology: is this a part of routine medical follow-up after radical pelvic radiotherapy?

Background:

Oncology follow-up has traditionally prioritised disease surveillance and the assessment and management of symptoms associated with cancer and its treatment. Over the past decade, the focus on late effects of treatment has increased, particularly those that have an adverse effect on long-term function and quality of life. The aim of this research was to explore factors that influence the identification of treatment-induced female sexual difficulties in routine oncology follow-up after radical pelvic radiotherapy.

Methods:

A structured observation schedule was used to systematically record topics discussed in 69 radiotherapy follow-up consultations observed over a 5-month period.

Results:

Analysis suggests that physical toxicity assessment focused on bowel (81%) and bladder (70%) symptoms. Vaginal toxicity was discussed less frequently (42%) and sexual issues were explored in only 25% of consultations. Formal recording of radiation toxicity through assessment questionnaires was limited to patients participating in clinical trials. Surveillance activity and the management of active physical symptoms predominated and psychosocial issues were addressed in only 42% of consultations.

Interpretation:

Female sexual morbidity after pelvic radiotherapy remains a neglected aspect of routine follow-up and cancer survivorship. Developments in both individual practice and service provision are necessary if the identification and management of treatment-induced female sexual difficulties is to be improved.     

Stereotactic body radiation therapy is effective and safe in patients with early-stage non-small cell lung cancer with low performance status and severe comorbidity

Background

The purpose of this study was to assess stereotactic body radiation therapy (SBRT) results and toxicity for stage I non-small cell lung cancer patients with low performance status and severe comorbidity.

Patients and Methods

From September 2008 to April 2010, 36 patients with 38 lesions were treated with hypofractionated SBRT. All except one were medically inoperable, had low performance status and/or severe cardiovascular and/or cardiopulmonary comorbidity. The patients were immobilized in an Elekta stereotactic body frame to improve setup accuracy, and four-dimensional CT scans were used for target delineation. Fractions of 15 Gy were prescribed to cover the planning target volume, giving a total dose of 45 Gy, with 1 fraction every second day. Cone beam CT was applied at each fraction to correct for setup errors. The patients were followed with toxicity evaluation and radiographic follow-up.

Results

Median follow-up time was 13.8 months (0–21 months). The local tumor control after 12 months was 100%. Four patients developed regional relapse about 12 months after SBRT. The 1-year disease-free survival was 83%. The median tumor shrinkage at 1 year was 22 mm. Three patients experienced systemic relapse after 13 months. One patient developed grade 3 chest pain toxicity and 16 patients reported temporary grade 1 chest pain toxicity. Two patients reported temporary increased dyspnea. No patient experienced a reduction of the performance status after SBRT.

Conclusion

SBRT is an effective and safe treatment modality for elderly patients with early-stage non-small cell lung cancer, having low performance status and severe comorbidity. It is possible to achieve high local control rates with good tolerance.Key Words: Early-stage non-small cell lung cancer, Stereotactic body radiation therapy, Low performance status, Severe comorbidity     

Multibeam inverse intensity-modulated radiotherapy (IMRT) for whole breast irradiation: a single center experience in China

Purpose

To present the clinical experience in our cancer center with multibeam inverse intensity-modulated radiotherapy (IMRT) for early stage breast cancer (BC) patients with whole breast irradiation (WBI).

Methods

We retrospectively analyzed 622 patients with Stage 0 to III BC treated from 2008 to 2011 with wide local excision and WBI, using an inverse IMRT technique. All of the patients were prescribed a total dose of 50 Gy to the whole breast in 2-Gy fractions, followed by a tumor bed boost of 10 Gy in 5 fractions using an electron beam.

Results

Of all of the patients, 132 (21.2%) received whole breast plus regional lymph node (RLN) irradiation. 438 of 622 patients had records of acute skin toxicity based on common terminology criteria (CTC) for adverse events. Two hundred eighty (64%) patients had Grade 0/1 toxicity, 153 (35%) had Grade 2 and only 4 patients experienced grade 3 toxicity. Seventy patients (16%) had moist desquamation. Univariate analysis revealed that breast planning target volume was the only predictive factor for Grade ≥2 acute dermatitis (P = 0.002). After 4 years, 170 patients reported cosmetic results by self-assessment, of whom 151 (89%) patients reported good/excellent cosmetic results, and 17 (11%) patients reported fair assessments. For invasive cancer, the four-year rate of freedom from locoregional recurrence survival was 98.3%. Regarding carcinoma in situ, no patients experienced recurrence.

Conclusion

BC patients who underwent conservative surgery followed by inverse IMRT plan exhibited acceptable acute toxicities and clinical outcomes. Longer follow-up is needed.     

A Safety and Survival Analysis of Neoadjuvant Bevacizumab with Standard Chemoradiation in a Phase I/II Study Compared with Standard Chemoradiation in Locally Advanced Rectal Cancer

Introduction.

Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchmark, we used data from an analysis of 42 patients with locally advanced rectal cancer treated with a contemporary approach of preoperative fluoropyrimidine-based radiation therapy.

Materials and Methods.

Outcome analyses were performed on 32 patients treated prospectively with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery as well as 42 patients treated with standard fluoropyrimidine-based chemoradiation.

Results.

Overall survival, disease-free survival, and local control showed favorable trends in patients treated with bevacizumab with chemoradiation followed by surgery. Acute and postoperative toxicity appeared acceptable.

Conclusions.

Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients.     

Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review

Background:

The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer.

Methods:

A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed.

Results:

Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects.

Conclusions:

Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.     

Outcomes of advanced and recurrent cervical cancer treated with cisplatin and generic topotecan: retrospective analysis in a tertiary care hospital in Thailand

Objective

Retrospective evaluation of the outcome of stage IVB, recurrent or persistent cervical cancer treated with cisplatin and generic topotecan (CT) in a tertiary care hospital in Thailand.

Methods

The medical records of patients treated with CT regimen at Chiang Mai University Hospital between January 2005 and December 2007 were reviewed and analyzed. The treatment protocol consisted of IV topotecan 0.75 mg/m² on days 1, 2, and 3; combined with cisplatin 50 mg/m² IV on day 1 and repeated every 21 days until progression or unacceptable toxicity for a maximum of 6 cycles. The outcomes were evaluated based on the response rate, progression free survival (PFS), and overall survival (OS) by using the World Health Organization criteria. The adverse effects of the treatments were also determined.

Results

Twenty-one cervical cancer patients received the CT regimen. The tumor response rate was 28.6%. The median PFS and OS was 4 and 11 months, respectively. With 87 cycles of chemotherapy, the most common grade 3 & 4 hematologic toxicity was neutropenia (57.9%).

Conclusion

Advanced and recurrent cervical cancer patients treated with cisplatin and generic topotecan had a favorable outcome with manageable toxicity.     

Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer

Background:

Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial.

Methods:

Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured.

Results:

Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers.

Conclusion:

This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.     

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer

Background:

Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.

Methods:

We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR).

Results:

In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD.

Conclusions:

Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.     

A prospective study of chemotherapy-induced febrile neutropenia in the South West London Cancer Network. Interpretation of study results in light of NCAG/NCEPOD findings

Background:

Chemotherapy-induced febrile neutropenia is a medical emergency complicating the treatment of many cancer patients. It is associated with considerable morbidity and mortality, as well as impacting on healthcare resources.

Methods:

A prospective study of all cases of chemotherapy-induced febrile neutropenia in the South West London Cancer Network was conducted over a 4-month period. Factors including demographics, treatment history, management of febrile neutropenia and outcome were recorded.

Results and conclusi:

Our results reflect those of the recent National Chemotherapy Advisory Group (NCEPOD, 2008)/National Confidential Enquiry into Patient Outcomes and Death reports (NCAG, 2009) and highlight the need for network-wide clinical care pathways to improve outcomes in this area.     

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 patients with stage ⅢB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results: A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. Conclusions: The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.