Non-Small Cell Lung Cancer : Therapeutic and Evolutionary Aspects in Cote d ’ Ivoire

Non-small cell lung cancer (NSCLC) is a heterogeneous group of malignancies including squamous cell carcinoma, adenocarcinoma, bronchioloalveolar carcinoma and large cell carcinoma. They are known to be of poor prognosis, despite a better understanding of bronchial oncogenesis. This descriptive retrospective study carried out over three years (January 2013 to December 31, 2016) at the Oncology Department of the Treichville University Hospital in Abidjan was aimed to assess the efficacy of new treatments for NSCLC in Cote d’Ivoire and to specify their benefit in terms of quality of life, comfort and overall survival. This 77 patients study, found that NSCLC, the most frequent of which is squamous cell carcinoma, occurs in relatively young subjects, smokers (91%) diagnosed at a locally advanced or metastatic stage (89%). Cisplatin base multi-drug chemotherapy was mostly used (71%). Combined all treatments, there was a significant clinical gain. However, no complete response was observed. Hematological and digestive toxicities were seen in more than 30% of cases. Overall survival was of 9 months on average. This study is an advocate to optimize primary prevention policies for a cancer with poor prognosis despite the development of new treatments such as target therapies.


Introduction
Broncho-pulmonary Cancer (BPC) is characterized by a cellular heterogeneity, of which non-small cells cancer is ranked first [1].This entity is considered to be assessment including an extended assessment (chest, abdominal and pelvic scan, abdominal ultrasound) and a biological assessment (CBC, liver and renal functions, calcemia) so as to minimizing possible treatment toxicities.At the end of this process, staging was established with the TNM system (2009) [5].The treatment instituted was either surgery or chemotherapy with cisplatin base regiments.Some patients had received exclusively symptomatic treatment (palliative radiation therapy, symptomatic care).For patients receiving chemotherapy, hyperhydration with added magnesium and potassium was necessary.The anticancer drugs were administered by either peripheral intravenous infusion or through an implantable venous access device and this every 21 days.
The response to treatment was evaluated according to the Recist 2000 criteria which define complete response (CR), partial response (PR), tumor stabilization (ST) and tumor progression (PT) [6].Tolerance was evaluated according to WHO criteria and overall survival according to the Kaplan Meier method [7].

Results
During our study period, 77 patients met the inclusion criteria.The average age was of 53 years with extremes of 41 and 70 years (Table 1).Male subjects were predominant (75% of cases) (Table 1).Tobacco abuse was found in 91% of cases (Table 1).Occupational exposure and family history were found in only 3% of cases each (Table 1).The clinical signs were polymorphic, chest pain being the major symptom in 87% of cases (Table 2).In 22% of cases, a paraneoplastic syndrome was found.The most common histological types were squamous cell  2).89% of our patients consulted at a locally advanced and metastatic stage (Table 2).
The most commonly used therapeutic modality was chemotherapy in approximately 71% of cases.The most commonly instituted protocol combined Taxane and Platine in 27% of cases.Target therapies were only used in 4% of cases (Table 3).All treatments combined, there was a significant clinical gain (Table 3).However, no complete response was observed.On the other hand, stabilization was observed especially with the combination Surgery-Chemotherapy     4).Post-chemotherapy toxicities were mainly haematological and digestive in more than 30% of cases (Table 5).These were usually Grade 2 WHO criteria; resolving spontaneously or with treatment.Overall survival was 09 months (Figure 1).

General Patients' Characteristics
The relative youth of the patients in our series is due to the socio-demographic characteristics of sub-Saharan African population.In Côte d'Ivoire, for example, the general census of the population carried out in 1998 and recently in 2014 showed that the Ivorian population was young [8].However, this characteristic  could also be explained by the ever increasing incidence of smoking (passive and active) in our country [9].Indeed, the between tobacco and the occurrence of non-small cell lung cancer has been established since the 1930s.Two large studies conducted one in the United States [10] and the other from general practitioners in Great Britain [11], have demonstrated the existence of a direct relationship between tobacco consumption and the occurrence of lung cancer with odds ratios of 9.1 -12.8 in humans and 2.1 -3.3 in women.NSCLC is essentially represented by squamous cell carcinoma.They are characterized by their clinical polymorphisms and are not correlated to any socio-cultural origin.

Therapeutic Aspects
Oncologic surgery is the therapeutic method that allows a definitive cure of NSCLC [12].This surgery, supplemented if necessary by radiotherapy, also ensures satisfactory regional control.It does not, however, treat metastatic progression, especially if there is an extensive lymph node involvement [13].Very few patients in our series received surgery and/or radiation therapy due to the advanced stage they were seen at.The factors related to this late diagnosis were multifaceted [3].These regiments have brought a significant gain to our patients and therefore an improvement in their quality of life.This improvement was also observed in various randomized trials comparing chemotherapy to exclusively symptomatic treatment.These studies have concluded to a significant advantage of chemotherapy versus symptomatic care [14].In addition to these commonly used anticancer drugs in our daily practice, certain so-called new molecules, more often used in the western series, have given hope to patients resistant to more traditional treatments [15] such as Pemetrexed.The efficacy of which has been proven in a non-inferiority phase III study by Scaglioti et al. [15].Targeted therapies were very rarely used in our series; due to their recent use in the management of NSCLC but also due to most of our patients' limited financial resources.However, Erlotinib, a tyrosine kinase inhibitor, has a recognized action in bronchopulmonary adenocarcinoma.In Western literature, other target therapies have already been tested in Phase III studies; Such as Cetuximab, which has shown benefits in first line treatment for metastatic NSCLC [16].As for Bevacizumab, its use has been slowed due to the occurrence of severe toxicities in some patients [17].

Tumor Response
The tumor response in our series was modest due to lack of financial resources making access to certain molecules difficult and poor observance of inter cure time.Moreover, this histological entity is deemed to be poorly chemo sensitive.
These results are seen in mostly African but also Western series [18].

The Tolerance Profile
The most frequent toxicities (hematological and digestive) are inherent to the different anticancer drugs used in our series.These were generally Taxanes with marked hematologic toxicity, especially in the white blood cell line [18].As for Cisplatin, which is a major drug in NSCLC-specific treatment, it was responsible for neurological and renal toxicities [14].The latter being almost constant, its administration requires hyperhydration with sodium and magnesium supplementation before and after chemotherapy [14].Regarding neurological toxicities, pure sensory neuropathy was consistently observed above the cumulative dose of 600 mg/m 2 [14].These different toxicities observed in our study were spontaneously reversible in the majority of the cases and for some with help of some treatments such as hematopoietic growths factors in some cases.

Conclusions
77 patients with NSCLC benefited from specific and/or non-specific therapies.
In this relatively young age group of patients, our protocols have brought a clinical gain with an acceptable tolerance profile.However, no improvement in overall survival was observed denoting the pejorative character of NSCLC.The focus must therefore be on effective primary prevention represented by an effective fight against tobacco abuse.
Efforts are currently being made in Côte d'Ivoire to establish programs to fight against smoking, to ban smoking in public places and tobacco advertisement.

Table 1 .
General characteristics of the population.

Table 2 .
Clinical and pathological Characteristics.

Table 3 .
Therapeutic modalities and clinical response.
T. Moctar et al.DOI: 10.4236/alc.2018.71001 5 Advances in Lung Cancer [19]al Survival did not exceed nine (09) months in our context.Lung cancer is considered to be of poor prognosis.The factors of poor prognosis most often observed in our patients were tumor size, lymph node involvement and metastatic spread.This pejorative prognosis is also found in Western literature where phase III studies have shown survival rates not exceeding 11 months[19].