Selecting patients for treatment with immunotherapy: Our experience in a resource-deprived economy

Background: Majority of the solid cancer patients seen in our Centers come with advanced diseases. Some of the cancers are locally advanced, while others are metastatic. Most of these patients who present late belong to the poverty-stricken group in our community. Only few of them can afford costly drugs for their treatment. The government Health Insurance Scheme does not cover cancer patients in Nigeria. Aim: To highlight the importance of immunotherapy in the management of metastatic cancers. Objective: We wish to share our experience in the use of immunotherapy (Bevacizumab) for metastatic cancers in the few patients who could afford the drug, and to highlight the need for reduction of the prices of immunotherapeutic drugs, or for government to subsidize the costs. Methods: From the 1,135 solid cancer patients treated in our two Centers in three years (February 2017 to January 2020), those who presented with metastasis were slated for immunotherapy after we had obtained their immunohistochemistry results. Results: Six hundred and one (601) patients (53.0%) presented late. Three hundred and fi ve (305) of these late presenters (50.7%) came with metastasis. Only 67 (22.0%) out of the 305 metastatic patients could afford immunotherapy, because of high cost. With the exception of one female patient, each of the remaining 66 patients was able to afford only one single dose of Bevacizumab (Avastin)R. Of these patients, one died of Tumor Lysis Syndrome following one single dose of 600 mg of Bevacizumab. There were measurable shrinkages of the tumor burdens, as well as improvement in the quality of life of the remaining 66 patients. Conclusion: Following these encouraging results, immunotherapy for metastatic carcinomas is to be encouraged for wider use, even in resource-deprived economies. Repeated doses will offer the patient greater benefi ts. Government should subsidize the cost of immunotherapeutic drugs so that they would become affordable by majority of those who need them. Research Article Selecting patients for treatment with immunotherapy: Our experience in a resourcedeprived economy Gabriel Chianakwana1*, Amobi Egwuonwu2, Christian Okoli2, Eric Ihekwoaba2, Dickson Emegoakor2, Henry Nzeako2, Evaristus Afi adigwe2 and Dan Anyiam3 1Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria and Gabro Specialist Hospital, Nnewi, Anambra State, Nigeria 2Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria 3Department of Histopathology/Morbid Anatomy, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria Received: 13 October, 2020 Accepted: 22 October, 2020 Published: 27 October, 2020 *Corresponding author: Gabriel Chianakwana, Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria and Gabro Specialist Hospital, Nnewi, Anambra State, Nigeria, Tel: +234-8065218169; E-mail:


Introduction
Cancer has remained a worldwide scourge, refusing to respect international boundaries or racial differences. The outcome of cancer treatment depends largely on the time of presentation by the patient.
Late presentation has remained the problem with the management of cancers. This situation is more common in developing countries, compared to patients in advanced countries who present early for treatment. The [5]. While tumor cells proliferate rapidly, they stimulate angiogenesis to provide oxygen and nutrient support after reaching a certain volume. Vascular endothelial growth factor (VEGF) signaling is an important target for cancer therapy because of its role in tumor angiogenesis, and its potential role in tumor cell survival and invasion. Bevacizumab acts as a monoclonal antibody against VEGF and can inhibit the formation of new vessels and tumor growth [6].
Immunotherapy has proved to be of great advantage in the treatment of metastatic breast carcinoma, especially when combined with chemotherapy [7][8][9][10], as well as in the treatment of metastatic colorectal carcinoma and hepatocellular carcinoma [10].

Results
Six hundred and one (601)     Each of these patients also received chemotherapy (Docetaxel), in addition to immunotherapy (Bevacizumab). There were measurable shrinkages of the tumor burdens, as well as improvement in the quality of life of the remaining 66 patients. Only seventeen (17) of the patients who received Bevacizumab are still alive as at 31 st July, 2020. The 238 patients with metastasis, who could not afford immunotherapy, had a more rapid, downward course in survival and in their quality of life, chemotherapy notwithstanding. One hundred and seven (107) of them died in hospital, while the remaining 131 (out of the 238 patients) were lost to follow-up.

Discussion
Different types of cancers have different biological propensities. Some cancers metastasis early while others metastasis late, depending on the grade of the cancer. Those that metastasize early are the anaplastic cancers which are so much in a hurry to spread, such that they do not have enough time to arrange their cells into any semblance of the type of tissue of origin. In breast cancer, for example, they display a very high Ki-67 Proliferative Index. This is associated with high grade of tumor, aggressive attitude of tumor, poor survival of patients, early recurrence of tumor, and metastasis [10].
Many more females were refl ected in this Study because majority of our patients were females with carcinoma of the breast. A few of them also had colorectal carcinoma. Majority of the male patients had colorectal carcinoma, with just two cases of carcinoma of the breast in males (an 84-year old retired civil servant, and a 42-year old trader).
The only female patient, a Nun, who was able to take Many previous studies [1][2][3][4] have shown that immunotherapy has the ability to increase survival rate and quality of life of patients, as well as to reduce the rate of recurrence of cancer.
Combination of chemotherapy with immunotherapy, as in this study, has also been shown by previous studies [8][9][10] to enhance survival of patients.

Conclusion
We conclude that immunotherapy has a benefi cial effect in metastatic cancers. This benefi cial effect is enhanced by the combination of chemotherapy with immunotherapy, and by repeated doses of this combination.

Recommendations
Reduction in the price of immunotherapeutic agents will enable more patients to acquire these truly priceless drugs.
The federal government's National Health Insurance Scheme (NHIS), as presently packaged, should be modifi ed to cover patients with cancer.
Further studies will be needed in our Centers, to objectively look at the effect of immunotherapy alone, compared with chemotherapy alone, in the treatment of metastatic cancers.