Small-cell carcinoma is a type of highly
malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
that most commonly arises within the
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
, although it can occasionally arise in other body sites, such as the
cervix
The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
,
prostate
The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...
,
and gastrointestinal tract. Compared to
non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.
Extensive stage small cell lung cancer is classified as a rare disorder. Ten-year relative survival rate is 3.5%; however, women have a higher survival rate, 4.3%, and men lower, 2.8%. Survival can be higher or lower based on a combination of factors including stage, age, gender and race.
Types of SCLC
Small-cell lung carcinoma has long been divided into two clinicopathological stages, termed ''limited stage'' (LS) and ''extensive stage'' (ES). The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal.
In general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be LS. If cancer has spread beyond that, it is said to be ES.
LS-SCLC
In cases of LS-SCLC,
combination chemotherapy
The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by t ...
(usually cisplatin or carboplatin plus etoposide) is administered together with concurrent chest
radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
(RT).
Chest RT has been shown to improve survival in LS-SCLC.
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
alone, with between 45% and 75% of individuals showing a "
complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s.
However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").
ES-SCLC
In ES-SCLC, platinum-based combination chemotherapy is the standard of care,
with radiotherapy added only to palliate symptoms such as
dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...
, pain from liver or bone metastases, or for treatment of
brain metastases
A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body and is therefore considered a secondary brain tumor. The metastasis typically shares a cancer cell type with the original site of the ...
, which, in small-cell
lung carcinoma
Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malignan ...
, typically have a rapid, if temporary, response to
whole brain radiotherapy
Whole brain radiotherapy (WBRT) is a palliative option for patients with brain metastases that alleviates symptoms, decreases the use of corticosteroids needed to control tumor-associated edema, and potentially improves overall survival.
Usage ...
.
Combination chemotherapy consists of a wide variety of agents, including
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
,
cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
,
vincristine
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...
and
carboplatin
Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...
. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, and the evidence surrounding the risk of treatment compared to the potential benefit of chemotherapy for people who have extensive SCLC is not clear.
[
If complete response to ]chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
occurs in a subject with SCLC, then prophylactic cranial irradiation
Prophylactic cranial irradiation (PCI) is a technique used to combat the occurrence of metastasis to the brain in highly aggressive cancers that commonly metastasize to brain, most notably small-cell lung cancer. Radiation therapy is commonly use ...
(PCI) is often used in an attempt to prevent the emergence of brain metastases
A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body and is therefore considered a secondary brain tumor. The metastasis typically shares a cancer cell type with the original site of the ...
. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years of follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.
In August 2018, the FDA approved nivolumab
Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urotheli ...
to treat patients with metastatic small cell lung cancer (SCLC) who failed to respond to platinum-based chemotherapy and at least one other line of treatment. Nivolumab is approved in more than 60 countries. According to LUNGevity Foundation, “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.”
In September 2018, the results from the global, randomized phase I/III IMpower 133 trial were announced at the World Congress on Lung Cancer in Toronto, ON. In this study, patients with ES-SCLC were treated with standard carboplatin plus etoposide and were randomized to receive atezolizumab
Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular ...
or placebo. Atezolizumab was associated with a significant improvement in overall survival (HR for death = 0.70)
Signs and symptoms
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.
Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...
, including adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
(ACTH) and anti-diuretic hormone
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
(ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH ca ...
(SIADH).
Lambert–Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.
Small-cell lung cancer
When associated with the lung, it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
. Caution is required when diagnosing SCLC because small cell mesothelioma – an extremely rare subtype of lung cancer – can be mistaken for small cell lung cancer.
It is thought to originate from neuroendocrine cell
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they b ...
s (APUD cell 350px, Actions of the major digestive hormones secreted by APUD cells
APUD cells (DNES cells) constitute a group of apparently unrelated endocrine cells, which were named by the scientist A.G.E. Pearse, who developed the APUD concept in the early ...
s) in the bronchus
A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus. ...
called Feyrter cells (named for Friedrich Feyrter).
Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
that may result in paraneoplastic syndromes and Cushing's syndrome.[ Approximately half of all individuals diagnosed with Lambert–Eaton myasthenic syndrome (LEMS) will eventually be found to have a small-cell carcinoma of the lung.]
Small-cell carcinoma is most often more rapidly and widely metastatic
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
than non-small-cell lung carcinoma
Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...
(and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes.
The mechanisms of its metastatic progression are not well-understood.
Combined small-cell lung carcinoma (c-SCLC)
Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer
Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
, including extremely complex malignant tissue admixtures.
When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
or adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma
Combined small cell lung carcinoma (or c-SCLC) is a form of multiphasic lung cancer that is medical diagnosis, diagnosed by a pathologist when a malignant tumor, arising from transformed cell (biology), cells originating in lung Tissue (biology), ...
(c-SCLC). C-SCLC is the only currently recognized subtype of SCLC.
Although combined small-cell lung carcinoma is currently staged and treated similarly to "pure" small-cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.
Smoking is a significant risk factor. Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes
A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
such as Lambert–Eaton myasthenic syndrome.
Extrapulmonary small-cell carcinoma
Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder. It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC. First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin. When the primary site is in the skin, it is referred to as a Merkel-cell carcinoma
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carci ...
.
Extrapulmonary small-cell carcinoma localized in the lymph nodes
This is an extremely rare type of small cell, and there has been little information in the scientific community. It appears to occur in only one or more lymph nodes, and nowhere else in the body. Treatment is similar to small cell lung cancer, but survival rates are much higher than other small-cell carcinomas.
Small-cell carcinoma of the prostate
Small-cell carcinoma of the prostate (SCCP) is a rare form of prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
(approx. 1% of PC). Due to the fact that there is little variation in prostate specific antigen
Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted b ...
levels, SCCP is normally diagnosed at an advanced stage, after metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
.
Symptomatic metastasis of SCCP to the brain is rare, and carries a poor prognosis.
Genetics
TP53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often ...
is mutated in 70 to 90% of SCLCs. RB1 and the retinoblastoma pathway are inactivated in most SCLCs. PTEN is mutated in 2 to 10%. MYC
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' ( MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes refe ...
amplifications and amplification of MYC family members are found in 30% of SCLCs. Loss of heterozygocity on chromosome arm 3p is found in more than 80% of SCLCs, including the loss of FHIT
Bis(5'-adenosyl)-triphosphatase also known as fragile histidine triad protein (FHIT) is an enzyme that in humans is encoded by the ''FHIT'' gene.
Function
FHIT is also known as human accelerated region 10. It may, therefore, have played a key ...
. One hundred translocations have so far been reported in SCLCs (see the "Mitelman Database" and the Atlas of Genetics and Cytogenetics in Oncology and Haematology
The Atlas of Genetics and Cytogenetics in Oncology and Haematology, created in 1997 by Jean-Loup Huret (with bioinformatics by Philippe Dessen) is a collection of resources on genes, Chromosome abnormality, chromosomes anomalies, leukemias, solid ...
,).
Diagnosis
When
* Localized: the cancer is confined to the lung (aka: limited stage SCLC).
* Regional: the cancer has spread to lymph nodes (or glands) within the chest (between limited and extensive stage SCLC). Lymph nodes act as a filtering system outside the lung, collecting cancer cells that are beginning to migrate out of the lung.
* Distant: the cancer has spread (or metastasized) to other parts of the body (aka: extensive stage SCLC).
At the time of diagnosis, 60–70% of people already have metastases.
Small-cell carcinoma is an undifferentiated neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
composed of primitive-appearing cells. As the name implies, the cells in small-cell carcinomas are smaller than normal cells, and barely have room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.
Treatment
Small-cell lung cancer is most commonly treated with a combination of two drugs, which is more effective than one drug alone.
Chemotherapy
# Cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
and etoposide
Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
,
# Carboplatin
Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...
and etoposide
Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
.
Cisplatin-resistance
The drug paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
may be useful in the treatment of cisplatin-resistant cancer. About 68.1% of cisplatin-resistant cells
appear to be sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells to
cisplatin. The mechanism for this activity is unknown. Paclitaxel-based chemotherapy showed modest activity in SCLC patients refractory to both etoposide- and camptothecin-based chemotherapy. The newer agent lurbinectedin
Lurbinectedin, sold under the brand name Zepzelca, is a medication used for the treatment of small cell lung cancer.
The most common side effects include leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased al ...
is active in relapsed SCLC and was approved for medical use in the United States in June 2020.[ ][ ]
Immunotherapy
In 2018, the FDA approved two immunotherapies for small cell lung cancer:
1. Nivolumab
Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urotheli ...
(Opdivo), and
2. Atezolizumab
Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular ...
(Tecentriq)
Funding controversy
Tecentriq treatment costs on average $13,200 per month, depending on the dosage schedule.
Despite updated data showing 30% more people with extensive stage small cell lung cancer
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...
are alive at 24 months compared to those who received chemotherapy alone, Canadian regulator had rejected to fund Tecentriq for extensive stage small-cell lung cancer "as too costly" followed by United Kingdom also citing "drug’s cost-effectiveness."
Radiation therapy
Chest radiation helps SCLC patients live longer by killing cancer cells and helping prevention of cancer recurrence. Another type of radiation, prophylactic cranial radiation, prevents central nervous system recurrence and can improve survival in patients with good performance status who have had a complete response or a very good partial response to chemoradiation in LD or chemotherapy in ED.
In case of relapse
If small cell lung cancer comes back after treatment, the following combination of drugs may be used as a salvage therapy:
# Cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
(Cytoxan, Procytox),
# Doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
(Adriamycin) and
# Vincristine
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...
(Oncovin)
# Paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
(Taxol)
# Irinotecan
Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisp ...
(Camptosar)
Current guidelines recommend that patients who relapse > 6 months from initial therapy should be retreated with the original chemotherapy regimen. For patients who relapse in < 6 months, single-agent chemotherapy either topotecan
Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form o ...
second-line therapy, or paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
can be used.
Novel agents
Several newer agents, including temozolomide
Temozolomide (TMZ), sold under the brand name Temodar among others, is a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma. Text was copied from this source which is © European Medicines Agency. Reproduction ...
and bendamustine
Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein.
Common s ...
, have activity in relapsed SCLC. Of note, temozolomide yielded a response rate of 38% for brain metastases due to SCLC.[
In a clinical trial of 50 patients, combination of ]olaparib
Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair ...
and temozolomide
Temozolomide (TMZ), sold under the brand name Temodar among others, is a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma. Text was copied from this source which is © European Medicines Agency. Reproduction ...
in relapsed small-cell lung cancer yielded an overall response rate of 41.7%, median progression-free survival 4.2 months, and overall survival was 8.5 months.
Lurbinectedin
Lurbinectedin, sold under the brand name Zepzelca, is a medication used for the treatment of small cell lung cancer.
The most common side effects include leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased al ...
is the most promising new agent that substantially increased overall survival rate in relapsed small cell lung cancer among sensitive disease patients. As a single agent, lurbinectedin demonstrated following clinical results in refractory small cell lung cancer
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...
trial:
:* Overall survival rate of 15.2 months for sensitive disease (chemotherapy-free interval of ≥ 90 days) with a disease control rate of 79.3% and overall response rate of 46.6%, and
:* Overall survival rate of 5.1 months for resistant (chemotherapy-free interval of < 90 days) with a disease control rate of 46.8% and overall response rate 21.3%.
Lurbinectedin is also being investigated in combination with doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
as second-line therapy in a randomized phase 3 trial. While overall survival in this trial is not yet known, response rates at second line were
:* 91.7% in sensitive disease with median progression-free survival of 5.8 months , and
:* 33.3% in resistant disease with median progression-free of 3.5 months.
Lurbinectedin is currently available in the U.S. under an expanded access program (EAP).[
]Trilaciclib
Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.
The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...
, a CKD4/6 inhibitor, reduces chemotheraphy-induced toxicity in patients being treated for small-cell lung cancer. Trilaciclib
Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.
The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...
’s developer, G1 Therapeutics
G1 Therapeutics, Inc. is an American biopharmaceutical company headquartered in Research Triangle Park, North Carolina. The company specializes in developing and commercializing small molecule therapeutics for the treatment of patients with cance ...
, makes the drug available in the U.S. under expanded access
Expanded access or compassionate use is the use of an unapproved drug or medical device under special forms of investigational new drug applications (IND) or IDE application for devices, outside of a clinical trial, by people with serious or life ...
while the FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
considers its New Drug Application (NDA). An approval decision on the NDA is expected by February 15, 2021. On February 12, 2021, the FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
approved trilaciclib
Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.
The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...
(brand name Cosela
Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.
The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increase ...
) as a treatment to reduce the frequency of chemotherapy-induced myelosuppression
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...
for patients receiving certain types of chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
for extensive-stage small-cell lung cancer.
Prognosis
5-year survival rates for small cell lung cancer (extensive and limited) range between 3.6% and 32.2% for women, and between 2.2% and 24.5% for men. Relative 5-year survival rate for both sexes has increased from 3.6% in 1975 to 6.7% in 2014.
Small-cell carcinoma is very responsive to chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
and radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse and median survival remains low. The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.
In ''limited-stage'' disease, relative 5-year survival rate (both sexes, all races, all ages) is 21.3%; however, women have higher 5-year survival rates, 26.9%, and men have lower survival rates, 21.3%.
The prognosis is far grimmer in ''extensive-stage'' small-cell lung carcinoma where 5-year relative survival rate (both sexes, all races, all ages) is 2.8%; however, women have higher 5-year survival rates, 3.4%, and men have lower 5-year survival rates, 2.2%.
Long-term survival of more than 5 years can be achieved with proper treatment. According to the 17th World Conference on Lung Cancer (WCLC), "patients who received chest radiation and prophylactic cranial irradiation along with a mean of five chemotherapy cycles could achieve a median survival of more than 5 years."
In some cases, long-term survival of 10+ years is achieved with chemotherapy and radiation alone.
5-year survival rates
The SEER database tracks 5-year relative survival rates based on age, sex, and race and is considered the most accurate source of survival information. This database uses terms "Localized," "Regional," and "Distant" to describe various stages of small cell lung cancer.
5-year relative survival rate for "both sexes" and "all races" affected by
* "Localized" small cell lung cancer is 28.5%;
* "Regional" small cell lung cancer 14.9%; and for
* "Distant" small cell lung cancer 2.9%.
Survival rates by sex
Women affected by small-cell lung cancer have higher 5-year survival rates than men.
* Localized: Women – 32.2% , Men – 24.5%
* Regional: Women – 17.0% , Men – 12.3%
* Distant: Women – 3.6% , Men – 2.2%
Survival rates by race, sex, age
5-year relative survival statistics are more accurate and, in some cases, higher when specific race and age range are combined with sex and stage at diagnosis. For example,
* Black / Female , Ages < 50 (at diagnosis) , Distant (ES SCLC) , = 7.0%.
* White / Female , Ages < 50 (at diagnosis) , Distant (ES SCLC) , = 6.1%
National Cancer Institute's SEER maintains publicly accessible database for specific survival rates.
Epidemiology
15% of lung cancers in the US are of this type. Small cell lung cancer occurs almost exclusively in smokers – most commonly in heavy smokers and rarely in non-smokers.
Recalcitrant Cancer Research Act
In 2013, the US Congress passed the Recalcitrant Cancer Research Act, which mandated increased attention to certain recalcitrant cancers, including small cell lung cancer. That led to the National Cancer Institute supporting small cell–specific research through a consortium.
As a result, new experimental drugs for small cell lung cancer are currently being tested, including Iadademstat ( ORY-1001) and Keytruda
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast can ...
(pembrolizumab
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast canc ...
).
Additional images
Image:Carcinoma microcellulare oatcell carcinoma or anaplastic carcinoma (lung)H&E magn 200x.jpg, Anaplastic (microcellular, oat cell) carcinoma from the lung (histopathology)
Image:Lung small cell carcinoma (2) by core needle biopsy.jpg, Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy.
Notable cases
* Dustin Diamond
Dustin Neil Diamond (January 7, 1977 – February 1, 2021) was an American actor and stand-up comedian, best known for his role as Samuel "Screech" Powers throughout the ''Saved by the Bell'' franchise.
Early life and family
Diamond was born in ...
, perhaps best known as an actor on Saved by the Bell.
See also
* Brown-Séquard syndrome
Brown-Séquard syndrome (also known as Brown-Séquard's hemiplegia, Brown-Séquard's paralysis, hemiparaplegic syndrome, hemiplegia et hemiparaplegia spinalis, or spinal hemiparaplegia) is caused by damage to one half of the spinal cord, i.e. hem ...
* Cervical cancer
Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
References
{{DEFAULTSORT:Small Cell Carcinoma
Carcinoma
Cytopathology
Infectious causes of cancer
Lung cancer
Rare diseases